Different treatment efficacies and T790M acquisition of EGFR-TKIs on NSCLC patients with variable Del-19 subtypes of EGFR.

EGFR exon 19 deletion (Del-19) comprises multiple advanced NSCLC subtypes. EGFR-tyrosine kinase inhibitor (TKI) efficacy and T790M acquisition in various Del-19 subtypes is unknown. We prospectively collected tissue samples from patients harboring NSCLC with Del-19 between 2006 and 2020. We evaluated EGFR-TKI treatment effectiveness among the different Del-19 subtypes. We collected 1391 NSCLC samples from 892 patients with Del-19, and the most common subtype was del E746-A750 (67.5%). 741 patients had taken first- or second-generation EGFR-TKIs. There were no significant differences in response rates between patients with different Del-19 subtypes (P = .630). Patients with indel E746 had the longest median PFS (14.6 months), but those with non-LRE deletions had the shortest PFS (8.9 months; P = .002). For OS analysis, patients with indel E746 also had the longest OS (34.1 months), but those with non-LRE deletions had the shortest OS (21.1 months; P = .046). Patients with different Del-19 subtypes showed no significant differences in the T790M acquisition rates (P = .443). Among the 151 patients with acquired T790M who received third-generation EGFR-TKIs, the Del-19 subtype was not associated with different RR and PFS. In vitro cellular viability and activation of the EGFR pathway analysis were consistent with the clinical findings. In conclusion, compared with del E746-A750, indel E746 was associated with longer PFS and OS, but the non-LRE subtype was correlated with shorter survival prognosis. There were no significant differences in the acquired T790M rate and treatment effectiveness of subsequent third-generation EGFR-TKIs between various Del-19 subgroups.

Activation of Toll-like receptor 3 inhibits HIV infection of human iPSC-derived microglia.

As a key immune cell in the brain, microglia are essential for protecting the central nervous system (CNS) from viral infections, including HIV. Microglia possess functional Toll-like receptor 3 (TLR3), a key viral sensor for activating interferon (IFN) signaling pathway-mediated antiviral immunity. We, therefore, studied the effect of poly (I:C), a synthetic ligand of TLR3, on the activation of the intracellular innate immunity against HIV in human iPSC-derived microglia (iMg). We found that poly (I:C) treatment of iMg effectively inhibits HIV infection/replication at both mRNA and protein levels. Investigations of the mechanisms revealed that TLR3 activation of iMg by poly (I:C) induced the expression of both type I and type III IFNs. Compared with untreated cells, the poly (I:C)-treated iMg expressed significantly higher levels of IFN-stimulated genes (ISGs) with known anti-HIV activities (ISG15, MxB, Viperin, MxA, and OAS-1). In addition, TLR3 activation elicited the expression of the HIV entry coreceptor CCR5 ligands (CC chemokines) in iMg. Furthermore, the transcriptional profile analysis showed that poly (I:C)-treated cells had the upregulated IFN signaling genes (ISG15, ISG20, IFITM1, IFITM2, IFITM3, IFITM10, APOBEC3A, OAS-2, MxA, and MxB) and the increased CC chemokine signaling genes (CCL1, CCL2, CCL3, CCL4, and CCL15). These observations indicate that TLR3 is a potential therapy target for activating the intracellular innate immunity against HIV infection/replication in human microglial cells. Therefore, further studies with animal models and clinical specimens are necessary to determine the role of TLR3 activation-driven antiviral response in the control and elimination of HIV in infected host cells.

LncRNA SLCO4A1-AS1 suppresses lung cancer progression by sequestering the TOX4-NTSR1 signaling axis.

BACKGROUND: Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms. METHODS: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1. RESULTS: SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion. CONCLUSION: These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer.

Geographical origin of Plasmodium vivax in the Hainan Island, China: insights from mitochondrial genome.

BACKGROUND: Hainan Province, China, has been an endemic region with high transmission of Plasmodium falciparum and Plasmodium vivax. Indigenous malaria caused by P. vivax was eliminated in Hainan in 2011, while imported vivax malaria remains. However, the geographical origin of P. vivax cases in Hainan remains unclear. METHODS: Indigenous and imported P. vivax isolates (n = 45) were collected from Hainan Province, and the 6 kb mitochondrial genome was obtained. Nucleotide (π) and haplotype (h) diversity were estimated using DnaSP. The numbers of synonymous nucleotide substitutions per synonymous site (dS) and nonsynonymous nucleotide substitutions per nonsynonymous site (dN) were calculated using the SNAP program. Arlequin software was used to estimate the genetic diversity index and assess population differentiation. Bayesian phylogenetic analysis of P. vivax was performed using MrBayes. A haplotype network was generated using the NETWORK program. RESULTS: In total, 983 complete mitochondrial genome sequences were collected, including 45 from this study and 938 publicly available from the NCBI. Thirty-three SNPs were identified, and 18 haplotypes were defined. The haplotype (0.834) and nucleotide (0.00061) diversity in the Hainan populations were higher than China's Anhui and Guizhou population, and the majority of pairwise FST values in Hainan exceeded 0.25, suggesting strong differentiation among most populations except in Southeast Asia. Most Hainan haplotypes were connected to South/East Asian and China's others haplotypes, but less connected with populations from China's Anhui and Guizhou provinces. Mitochondrial lineages of Hainan P. vivax belonged to clade 1 of four well-supported clades in a phylogenetic tree, most haplotypes of indigenous cases formed a subclade of clade 1, and the origin of seven imported cases (50%) could be inferred from the phylogenetic tree, but five imported cases (42.8%) could not be traced using the phylogenetic tree alone, necessitating epidemiological investigation. CONCLUSIONS: Indigenous cases in Hainan display high genetic (haplotype and nucleotide) diversity. Haplotype network analysis also revealed most haplotypes in Hainan were connected to the Southeast Asian populations and divergence to a cluster of China's other populations. According to the mtDNA phylogenetic tree, some haplotypes were shared between geographic populations, and some haplotypes have formed lineages. Multiple tests are needed to further explore the origin and expansion of P. vivax populations.

Assembly and co-occurrence patterns of rhizosphere bacterial communities are closely linked to soil fertility during continuous cropping of cut chrysanthemum (Chrysanthemum morifolium Ramat).

AIMS: Continuous cropping is known to have profound effects on the soil microbial community in different planting systems. However, we lack an understanding of how different years of continuous cropping affects rhizosphere soil bacterial community co-occurrence pattern and assembly processes in the cut chrysanthemum (Chrysanthemum morifolium Ramat.) field. METHODS AND RESULTS: We collected the soils from cut chrysanthemum rhizospheres with planting for 1 year (PY1) and continuous cropping for 6 years (CY6) and 12 years (CY12). Real-time quantitative PCR and flow cytometry (FCM) techniques were used to test the 16S rRNA gene copy number and bacterial cell count, respectively. The bacterial community structure was analysed by using high-throughput sequencing technology. The CY12 had a significantly decreased soil fertility index and rhizosphere bacterial living cell counts and gene copy numbers compared to CY6 and PY1 (P < 0.05). The rhizosphere bacterial community dissimilarity increased as the continuous cropping years increased. Three main ecological clusters (modules #1, #2, and #3) were observed in the bacterial co-occurrence network across all samples, and only the relative abundance of module #1 (enriched in the CY12) was significantly correlated with soil fertility (P < 0.05). Moreover, the rhizosphere bacterial community assembly was primarily governed by the deterministic process under 12 years of continuous cropping. CONCLUSIONS: Soil fertility decline correlates with ecological network modularization and the deterministic assembly process of the rhizosphere bacterial community of cut chrysanthemum during continuous cropping.

Fucoidan with three functions extracted from Sargassum aquifolium integrated rice-husk synthesis dual-imaging mesoporous silica nanoparticle.

In this study, we used the nanoparticle delivery system to reduce the side effect of conventional cancer treatment- radiation therapy and chemotherapy. We used rice husk silicon source mesoporous silica nanoparticle doped in Eu3+ and Gd3+ as the carrier in the delivery system and to enable fluorescence and MRI dual-imaging functions for follow-up therapy. In addition, we choose a popular seaweed extract-fucoidan was extracted from the same brown algae-Sargassum aquifolium collected from Taiwan-Pingtung-Kenting-Chuanfan Rock. In this research, we used acid hydrolysis to prepared two different molecular weight fucoidan, the small molecular fucoidan (Fus) as drug, and the molecular weight approximately 1 kDa fucoidan (Ful) as the nanoparticle gatekeeper, and as targeting molecule for overexpressed P-selectin on the surface of the metastatic tumors. The results of the cell cytotoxicity experiment showed that HCT116 cancer cells have a survival rate of approximately 58.12% when treated with 200 µg/mL fucoidan. Dual-imaging rice husk mesoporous silica nanoparticles (rMSN-EuGd) were modified with 1 kDa fucoidan (Ful) as the gatekeeper and target, and the small molecule fucoidan (Fus) was loaded into nanoparticles (Ful-Fus@rMSN-EuGd) at a concentration of 200 µg/mL. The HCT116 cancer cells had a survival rate of approximately 55.56%. The cell cytotoxicity experiment results show that Ful-Fus@rMSN-EuGd can improve the anticancer effect of fucoidan, and the nanoparticle drug delivery system using fucoidan as a drug, target, and gatekeeper was successfully synthesized.

Prognostic value of early and late spontaneous conversion into a shockable rhythm for patients with out-of-hospital cardiac arrest.

BACKGROUND: The prognostic significance of conversion into a shockable rhythm in patients who experienced out-of-hospital cardiac arrest (OHCA) with an initially nonshockable rhythm is controversial, perhaps due to the timing of rhythm conversion not being considered previously. We aimed to compare the different prognoses of patients with OHCA and early and late conversion of their rhythm into a shockable rhythm. METHODS: This was a single-centre retrospective cohort study. We enrolled patients with OHCA who were sent to a medical centre in central Taiwan from 2016 to 2020. Patients <18 years old, those with cardiac arrest due to trauma or a circumstantial cause, and those for whom resuscitation was not attempted were excluded. Patients were divided into two groups in accordance with presentation with an initially shockable rhythm. Those with an initially nonshockable rhythm were divided into three subgroups: early-conversion, late-conversion, and nonconversion groups. The primary outcome was the neurological functional status upon discharge from hospital. RESULTS: A total of 1645 patients with OHCA were included: initially shockable rhythm group, 339; early conversion group, 68; late-conversion group, 166; and nonconversion group, 1072. After adjustment, multivariate logistic regression revealed that a favourable neurological outcome was more common in the early conversion group than the nonconversion group (odds ratio [OR] 2.4; 95% confidence interval [CI], 1.1-5.3; p = 0.035), whereas the late-conversion group did not significantly differ from the nonconversion group (OR 0.5; 95% CI, 0.1-1.5; p = 0.211). The proportions of sustained return of spontaneous circulation and survival to discharge were also higher in the early conversion group than the late-conversion group (OR 2.9 95% CI 1.6-5.5, p = 0.001 and OR 4.5, 1.8-11.0, p = 0.001, respectively). CONCLUSION: In patients who experience OHCA and have an initially nonshockable rhythm, early conversion into a shockable rhythm resulted in a better prognosis, whereas late conversion was not significantly different from nonconversion.

Vascular ring and sling in a fetus who developed esophageal and airway compression after birth.

Vascular ring and sling are congenital anomalies of the vascular structure in the thorax with a prevalence of 2.4/10,000 live births. Double aortic arch (DAA), right aortic arch with left ductus arteriosus and aberrant left subclavian artery (RAA-ALSA), and pulmonary artery sling (PAS) are the three common types of vascular ring and sling. These anomalies can be isolated or accompanied by intracardiac malformation. The presence of both vascular ring and PAS is extremely rare. Here, we report a fetus who was prenatally diagnosed with PAS and RAA-ALS, and developed symptoms due to esophageal and airway compression after birth.

Acquired resistance to EGFR tyrosine kinase inhibitors is mediated by the reactivation of STC2/JUN/AXL signaling in lung cancer.

Constitutive activation of the epidermal growth factor receptor (EGFR) signaling pathway is implicated in the initiation and progression of lung cancer. EGFR tyrosine kinase inhibitor (TKI)-targeted therapy has become the standard treatment for nonsmall cell lung cancer (NSCLC) patients. However, acquired resistance to these agents remains a major obstacle for managing NSCLC. Here, we investigated a novel strategy to overcome EGFR TKI resistance by targeting the stanniocalcin 2 (STC2)-JUN-AXL pathway. We revealed that STC2 was expressed at significantly higher levels in EGFR TKI-resistant cells. Further, clinical analysis showed that STC2 expression was increased after the development of EGFR TKI resistance and that higher levels were correlated with shorter progression-free survival in EGFR TKI-treated lung cancer patients. Moreover, STC2 overexpression in EGFR TKI-sensitive cells resulted in EGFR TKI resistance. Conversely, genetic silencing of STC2 rendered EGFR TKI-resistant cells more sensitive to EGFR TKIs. Mechanically, STC2 enhanced AXL promoter activity by increasing the phosphorylation of c-Jun, which is an indispensable transcription factor that transactivates AXL. STC2 promoted activation of the JUN-AXL-extracellular signal-regulated kinase (ERK) signaling axis in lung cancer cells. Pharmacological or genetic inhibition of AXL-ERK activity inhibited STC2-mediated EGFR TKI resistance. We also demonstrated that PE2988 cells, a C797S-independent osimertinib-resistant primary cancer cell line from a lung cancer patient, responded to combined AXL inhibitor and osimertinib treatment. In conclusion, our research indicates that STC2 overexpression is important for acquired resistance to EGFR TKIs and that STC2-JUN-AXL-ERK signaling might be a potential therapeutic target to overcome resistance to EGFR TKIs.

A comparison of two centrifuge techniques for constructing vulnerability curves: insight into the 'open-vessel' artifact.

A vulnerability curve (VC) describes the extent of xylem cavitation resistance. Centrifuges have been used to generate VCs for decades via static- and flow-centrifuge methods. Recently, the validity of the centrifuge techniques has been questioned. Researchers have hypothesized that the centrifuge techniques might yield unreliable VCs due to the open-vessel artifact. However, other researchers reject this hypothesis. The focus of the dispute is centered on whether exponential VCs are more reliable when the static-centrifuge method is used rather than the flow-centrifuge method. To further test the reliability of the centrifuge technique, two centrifuges were manufactured to simulate the static- and flow-centrifuge methods. VCs of three species with open vessels of known lengths were constructed using the two centrifuges. The results showed that both centrifuge techniques produced invalid VCs for Robinia because the water flow through stems under mild tension in centrifuges led to an increasing loss of water conductivity. In addition, the injection of water in the flow-centrifuge exacerbated the loss of water conductivity. However, both centrifuge techniques yielded reliable VCs for Prunus, regardless of the presence of open vessels in the tested samples. We conclude that centrifuge techniques can be used in species with open vessels only when the centrifuge produces a VC that matches the bench-dehydration VC.

Development and validation study of a non-alcoholic fatty liver disease risk scoring model among adults in China.

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in China. It is usually asymptomatic and transabdominal ultrasound (USS) is the usual means for diagnosis, but it may not be feasible to have USS screening of the whole population. Objective: To develop a risk scoring model for predicting the presence of NAFLD using parameters that can be easily obtain in clinical settings. Methods: A retrospective study on the data of 672 adults who had general health check including a transabdominal ultrasound. Fractional polynomial and multivariable logistic regressions of sociodemographic and biochemical variables on NAFLD were used to identify the predictors. A risk score was assigned to each predictor using the scaled standardized ß-coefficient to create a risk prediction algorithm. The accuracy for NAFLD detection by each cut-off score in the risk algorithm was evaluated. Results: The prevalence of NAFLD in our study population was 33.0% (222/672). Six significant factors were selected in the final prediction model. The areas under the curve (AUC) was 0.82 (95% CI: 0.78-0.85). The optimal cut-off score, based on the ROC was 35, with a sensitivity of 76.58% (95% CI: 70.44-81.98%) and specificity of 74.89% (95% CI: 70.62-78.83%). Conclusion: A NAFLD risk scoring model can be used to identify asymptomatic Chinese people who are at risk of NAFLD for further USS investigation.

Zoom lens design for 10.2-megapixel APS-C digital SLR cameras.

A zoom lens design for a 10.2-megapixel digital single-lens reflex (SLR) camera with an advanced photo system type-C (APS-C) CCD image sensor is presented. The proposed zoom lens design consists of four groups of 3× zoom lenses with a focal length range of 17-51 mm. In the optimization process, 107 kinds of Schott glass combined with 26 kinds of plastic materials, as listed in Code V, are used. The best combination of glass and plastic materials is found based on the nd-Vd diagram. The modulation transfer function (MTF) was greater than 0.509 at 42 lp/mm, the lateral chromatic aberration was less than 5 µm, the optical distortion was less than 1.97%, and the relative illumination was greater than 80.05%. We also performed the tolerance analysis with the 2σ (97.7%) position selected and given tolerance tables and results for three zooming positions, which made the design more practical for manufacturing.

Comparison of Two New Traps To the Biogents BG-Sentinel Trap For Collecting Aedes albopictus In North Florida.

Multiple surveillance traps are currently available for adult mosquito surveillance. In this study, 2 new types, the Maxttrac™ Uno and Maxttrac™ Breeze mosquito traps, were compared against the BioGents™-Sentinel trap (BGS) for overall success in collecting Aedes albopictus in a 1,027-m2 vehicle enclosure and in the field. The enclosure test results showed both traps collected significantly fewer Ae. albopictus, compared to the BGS trap. The modification of using all BG lures for each trap did not increase the number of mosquitoes collected in the 2 new traps, when compared to collection with the original lures tested in the vehicle enclosure. Field test results showed that BGS trap collected higher numbers of Ae. albopictus than the 2 new traps, regardless of switching lure or not. Overall, the BGS trap was the most effective trap and the 2 new traps could be used as additional tools for the collection of Ae. albopictus.

Neighborhood Frequency Effect in Chinese Word Recognition: Evidence from Naming and Lexical Decision.

Neighborhood frequency is a crucial variable to know the nature of word recognition. Different from alphabetic scripts, neighborhood frequency in Chinese is usually confounded by component character frequency and neighborhood size. Three experiments were designed to explore the role of the neighborhood frequency effect in Chinese and the stimuli were all two-character words. This effect was evaluated on targets with- and without-higher frequency neighbors with neighborhood size matched. Among the experiments, the patterns of the leading character frequency effect and word frequency effect in the naming and lexical decision tasks were compared. The results implied an inhibitory neighborhood frequency effect in Chinese word recognition. Accordingly, a possible cognitive mechanism of the neighborhood frequency effect was thus proposed.

[Effects of Tengmei Decoction on the PPAR-y/NF-KB Signaling Pathway in Synovium of Collagen-in- duced Arthritis Rats].

Objective To observe the effects of Tengmei Decoction (TMD) on the expressions of peroxisome proliferator activated receptor gamma (PPARγ) , nuclear factor kappa B (NF-κB) , and IL- 17 in synovium of collagen-induced arthritis (CIA) rats, and to study its molecular mechanismpf. inhibi- ting synovial immune inflammatory injuries. Methods CIA model was established in Sprague-Dawley rats. Successfully modeled rats were randomly divided into the model group, the positive drug ,oup, high and low dose TMD groups, 6 in each group. Besides, a normal group was set up (n =6). Deionized water (10 mL . kg⁻¹ . d⁻¹) was administrated to rats in the normal group and the model group by gastro- gavage. Leflunomide (1. 87 mg . kg ⁻¹ . d ⁻¹) was administrated to rats in the positive drug group by gastro- gavage. TMD (31. 8 g crude drugs . kg ⁻¹ . d ⁻¹ and 15. 9 g crude drugs . kg ⁻¹ . d ⁻¹) was administrated to rats in high and low dose TMD groups respectively by gastrogavage. The intervention lasted for 12 suc- cessive weeks. Protein and mRNA levels of PPARy, P65, and IL-17 were detected at the end of intervention. Results Compared with the normal group, mRNA and protein expression levels of PPARγ, P65, and IL-17 were up-regulated in the model group (P <0. 01). Compared with the model group, PPARγ pro- tein expression level was up-regulated, mRNA and protein expression levels of P65 and IL-17 were down-regulated in high dose TMD group (P <0. 01). mRNA and protein expression levels of PPARγ were up-regulated, mRNA and protein expression levels of P65 and IL-17 were down-regulated in the positive drug group and low dose TMD group (P <0. 01). Conclusions TMD could ameliorate pathological damage of joint synovium , and inhibit expressions of immune inflammatory factors.

Heparin co-factor II enhances cell motility and promotes metastasis in non-small cell lung cancer.

Using the Serial Analysis of Gene Expression (SAGE) database from the Cancer Genome Anatomy Project, we identified heparin co-factor II (HCII), which is over-expressed in non-small cell lung cancer (NSCLC). Here, we investigated the clinical significance of HCII and provided molecular evidence to support the suggestion that HCII could enhance cancer metastasis in NSCLC. We found that high HCII expression in tumour tissue was associated with increased cancer recurrence and shorter overall survival times in 75 clinically operable NSCLC patients. High pretreatment plasma concentration of HCII was associated with reduced overall survival in 57 consecutive NSCLC patients. We over-expressed and knocked down HCII expression in lung cancer cell lines and confirmed that HCII could promote cell motility, invasion ability and filopodium dynamics in NSCLC cells in vitro and increased metastatic colonization in an in vivo mouse model. Exogenous treatment of HCII promoted cancer cell migration, and this promigratory effect of HCII was independent of thrombin. We further showed that HCII could up-regulate cancer cell migration through the activation of PI3K, which acts upstream of Rac1 and Cdc42, and this effect could be blocked by heparin. We suggest that HCII is a novel metastasis enhancer and may be used as a prognostic predictor for heparin treatment in NSCLC.

Genetic diversity of Plasmodium vivax population before elimination of malaria in Hainan Province, China.

BACKGROUND: Hainan Province is one of the most severe endemic regions with high transmission of Plasmodium falciparum and Plasmodium vivax in China. However, the incidence of P. falciparum and P. vivax has dropped dramatically since 2007 and a national elimination malaria programme (NEMP) was launched after 2010. To better understand the genetic information on P. vivax population before elimination of malaria in Hainan Province, the extent of genetic diversity of P. vivax isolates in Hainan Province was investigated using four polymorphic genetic markers, including P. vivax merozoite surface proteins 1, 3α, and 3ß (pvmsp-1, pvmsp-3α, and pvmsp-3ß) and circumsporozoite protein (pvcsp). METHODS: Isolates of P. vivax (n = 27) from Hainan Province were collected from 2009 to 2010 and pvmsp-1 and pvcsp were analysed by DNA sequencing, respectively. Using polymerase chain reaction-restriction fragment length polymorphism were analysed in pvmsp-3α, and pvmsp-3ß. RESULTS: The DNA sequencing analysis on pvmsp1 revealed that there were three allele types: Salvador-1 (Sal-1), Belem and recombinant (R) types. Among them, Sal-1 type was a dominant strain with eight variant subtypes (88.9%), whereas R- (3.7%) and Belem-type strains (7.4%) had one variant subtypes, respectively. All the isolates carried pvcsp with VK210 type accounting for 85.2% (23/27 isolates) and VK247 type accounting for 14.8% (4/27). Only type A and type B alleles were successfully amplified in pvmsp-3α gene, and a high level of polymorphism was observed in pvmsp-3α. Considering pvmsp-3ß gene, type A was the predominant type in 17 isolates (63%), whereas type B was dominant in only ten isolates (37%). CONCLUSION: The present data indicate that there was high degree of genetic diversity among P. vivax population in Hainan Province of China during the pre-elimination stage of malaria, with 26 unique haplotypes observed among 27 samples.

Sensitivity of Plasmodium falciparum to antimalarial drugs in Hainan Island, China.

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time (22.5 ± 10.6 hr) and the mean parasite clearance time (27.3 ± 12.2 hr) showed no statistical significance with different genders, ages, temperatures, or parasite density (P > 0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (P < 0.0001). The resistance intensities decreased as follows: chloroquine > piperaquine > pyronarididine > artesunate. The inhibitory dose 50 (IC50) was 3.77 × 10(-6) mol/L, 2.09 × 10(-6) mol/L, 0.09 × 10(-6) mol/L, and 0.05 × 10(-6) mol/L, and the mean concentrations for complete inhibition (CIMC) of schizont formation were 5.60 × 10(-6) mol/L, 9.26 × 10(-6) mol/L, 0.55 × 10(-6) mol/L, and 0.07 × 10(-6) mol/L, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.