Polyketides with α-glucosidase inhibitory and neuroprotective activities from Aspergillus versicolor associated with Pedicularis sylvatica.

Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.

Quality control and external quality assessment for the independent clinic-based evaluation of point-of-care testing to detect Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in eight countries.

BACKGROUND: Sexually transmitted infections caused by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) remain significant global health problems. The World Health Organization (WHO) has recently conducted a multi-faceted, multi-country validation study (ProSPeRo), which included an evaluation of the Xpert CT/NG and Xpert TV assays on the GeneXpert system (Cepheid, Sunnyvale, Ca., USA) in clinic-based settings across eight countries. To support the study, a training and quality management system was implemented and evaluated. METHODS: A comprehensive training program for the study was developed. Quality control (QC) and external quality assessment (EQA) samples were provided by an accredited quality assurance provider. QC testing was conducted at 14 point-of-care testing (POCT) clinics, while EQA samples were tested by the POCT sites and a reference laboratory supporting each clinic. RESULTS: For QC testing, concordance with the expected results for CT and NG was > 99% and rates of unsuccessful tests were < 4%. For TV testing, concordance was similar (97%), but rates of unsuccessful tests were high (18%), particularly in the 'TV negative' sample. For EQA testing initially conducted in 2018, concordance was 100% for CT and NG, and 90% for TV for the reference laboratory group (which used non-GeneXpert systems). Concordance for the POCT group was also high (> 94%) for all analytes, but this cohort (which used GeneXpert systems) exhibited a high rate of unsuccessful TV tests. All but one of these unsuccessful tests was subcategorised as 'invalid'. CONCLUSIONS: The high level of concordance for QC and EQA testing confirm that the trained operators at the POC clinical sites were competent to conduct POC testing and that the training and quality systems implemented for the ProSPeRo study were effective. The quality materials used were satisfactory for CT and NG but exhibited poor performance for TV testing on the GeneXpert system. The WHO should continue to work with industry and EQA providers to provide improved materials that are reliable, stable and cost effective for quality management, as it seeks to rollout molecular-based STI POCT in non-laboratory-based settings. TRIAL REGISTRATION: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee.

Synthesis, structure, theoretical calculation and antibacterial property of two novel Zn(II)/Ni(II) compounds based on 3, 5-dichlorosalicylaldehyde thiocarbamide ligand.

Two new compounds namely [Zn(L1)phen]31 and Ni(L1)phen(MeOH) 2 (L1 = 3, 5-dichlorosalicylaldehyde thiosemicarbazone) were synthesized by the slow evaporation method at room temperature. The structure of ligand L1 was determined using 1H NMR and 13C NMR spectra. X-ray single crystal diffraction analysis revealed that compounds 1-2 can form 3D supramolecular network structures through π···π stacking and hydrogen bonding interactions. The DFT calculation shows that the coordination of ligand and metal is in good agreement with the experimental results. Hirshfeld surface analysis revealed that H…H and Cl…H interactions were the predominant interactions in compounds 1-2. Energy framework analysis indicated that dispersion energy played a dominant role in the energy composition of compounds 1-2. The inhibitory effects of compounds 1-2 against Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA) were tested using the paper disk diffusion method (1: E. coli: 18 mm, MRSA: 17 mm, 2: E. coli: 15 mm, MRSA: 16 mm). Ion releasing experiments were conducted to assess the ion release capacity of compounds 1-2 (Zn2+, 4 days, 38.33 µg/mL; Ni2+, 4 days, 29.12 µg/mL). Molecular docking demonstrated the interaction modes of compounds 1-2 with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and dihydrofolate reductase (DHFR) in bacteria, involving hydrophobic, stacking, hydrogen bonding and halogen bonding interactions. The generation of reactive oxygen species (ROS) in bacteria under the presence of compounds 1-2 were evaluated using a fluorescent dye known as dichlorodihydrofluorescein diacetate (DCFH-DA). Potential antibacterial mechanisms of compounds 1-2 were proposed.

The ratio of neutrophils to lymphocytes effectively predicts clinical outcomes in idiopathic membranous nephropathy.

BACKGROUND: Systemic inflammatory indicators are important in the prognoses of various diseases. Such indicators, including the neutrophil-to-lymphocyte ratio (NLR), can be meaningful in predicting the clinical outcome in patients diagnosed with idiopathic membranous nephropathy (IMN). MATERIALS AND METHODS: 112 IMN patients diagnosed by renal biopsy were recruited retrospectively. The endpoint was defined as a combination of partial and complete remission. Statistical analysis determined the independent factors associated with clinical remission and the predictive utility of NLR. RESULTS: Within the 12-month follow-up period, 72 patients achieved clinical remission after treatment. Univariate analysis identified significant differences in serum albumin, estimated glomerular filtration rate (eGFR), proteinuria, neutrophil count, and NLR between the remission group and the non-remission group (all p < 0.05). Cox proportional hazards indicated that elevated eGFR (HR 1.022, 95% CI (1.009 - 1.035), p = 0.001), lower NLR (HR 0.345, 95% CI (0.237 - 0.501), p = 0.0001), and decreased proteinuria (HR 0.826, 95% CI (0.693 - 0.984), p = 0.032) were protective elements for remission. With an optimal cut-off value of 2.61, the pre-treatment NLR had an excellent ability to identify the remission (area under the curve (AUC), 0.785). Participants were separated into low- and high-NLR groups by using 2.61. Kaplan-Meier survival curves revealed significantly higher remission rates in the lower group (p < 0.0001). CONCLUSION: The NLR is an effective indicator for predicting clinical remission in patients with IMN.

Roxadustat Versus Erythropoietin: The Comparison of Efficacy in Reversing Ventricular Remodeling in Dialysis Patients with Anaemia.

Background: Renal anaemia and left ventricular hypertrophy are the main complications of chronic kidney disease and are shared among dialysis patients. This retrospective study aimed to compare the efficacies of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat and recombinant human erythropoietin in reversing ventricular remodeling in dialysis patients with renal anaemia. Methods: A total of 204 participants underwent baseline examinations, including echocardiograms and laboratory tests, before being administered either treatment for at least 24 weeks from January 2018 to October 2021, after which follow-up examinations were conducted at 6 months. Propensity score matching based on key variables included age, gender, cardiovascular diseases, cardiovascular medications, dialysis course and the vascular access at baseline was performed to include populations with similar characteristics between groups. Results: In total, 136 patients were included with roxadustat or recombinant human erythropoietin. The left ventricular mass index after treatment with roxadustat and recombinant human erythropoietin both significantly decreased after 6 months, but there was no significant difference in the change in left ventricular mass index between the two groups. In addition, the left ventricular end-diastolic diameters and left ventricular wall thickness, systolic blood pressure, and diastolic blood pressure significantly decreased in the roxadustat group. Roxadustat and recombinant human erythropoietin also increased haemoglobin significantly, but there was no significant difference in the change in haemoglobin between the two groups. The results of multiple linear regression showed that the change in haemoglobin was independent factor affecting the improvement of left ventricular mass index. Conclusions: The increase of haemoglobin was associated with improving left ventricular hypertrophy in dialysis patients. However, the beneficial effects between roxadustat and recombinant human erythropoietin on left ventricular mass index did not show clear superiority or inferiority in six months.

The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint.

The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to other members of the Coronaviridae family. We also show that these spike NTD (S-NTD) proteins adhere to Calu3 cells, a human lung cell line, although the biological relevance of this is unclear. In contrast to what has been shown for Middle East respiratory syndrome coronavirus (MERS-CoV), which attaches sialic acids during cell entry, sialic acids present on Calu3 cells inhibited sarbecovirus infection. Therefore, while sarbecoviruses can interact with cell surface glycans similarly to other coronaviruses, their reliance on glycans for entry is different from that of other respiratory coronaviruses, suggesting sarbecoviruses and MERS-CoV have adapted to different cell types, tissues, or hosts during their divergent evolution. Our findings provide important clues for further exploring the biological functions of sarbecovirus glycan binding and adds to our growing understanding of the complex forces that shape coronavirus spike evolution. IMPORTANCE Spike N-terminal domains (S-NTD) of sarbecoviruses are highly diverse; however, their function remains largely understudied compared with the receptor-binding domains (RBD). Here, we show that sarbecovirus S-NTD can be phylogenetically clustered into five clades and exhibit various levels of glycan binding in vitro. We also show that, unlike some coronaviruses, including MERS-CoV, sialic acids present on the surface of Calu3, a human lung cell culture, inhibit SARS-CoV-2 and other sarbecoviruses. These results suggest that while glycan binding might be an ancestral trait conserved across different coronavirus families, the functional outcome during infection can vary, reflecting divergent viral evolution. Our results expand our knowledge on the biological functions of the S-NTD across diverse sarbecoviruses and provide insight on the evolutionary history of coronavirus spike.

Knowledge on Chlamydia trachomatis and Acceptance to Testing for It Among Young Students in China.

BACKGROUND: Actively screening for Chlamydia trachomatis (CT) is important for young people because of a high prevalence of asymptomatic infection in this population. This study aimed to investigate knowledge on CT and preference to the screening services for CT among young students in China. METHODS: From June to July 2022, a web-based questionnaire survey was conducted to collect information on sociodemographic characteristics, sexual behaviors, knowledge of CT, previous testing for CT, and preference to platform of testing for CT among Chinese young students. An online home-based self-sampling test (HBSST) service was offered free of charge if the participant was willing to be tested for CT. Statistical analyses included descriptive analysis, χ 2 test, and multivariable logistic regression. RESULTS: Of 520 participants, 419 (80.6%) were aged between 16 and 24 years, 235 (45.2%) reported having sexual experience in the past, and 27 (5.2%) being tested before for CT. Slightly higher than 10% (57/520) of students were knowledgeable about CT. About one-third (36.9%) expressed their willingness to have a testing for CT but majority of them (63.1%) preferred to a free testing. Having sexual experience was significantly associated with the willingness to take the HBSST service (adjusted odds ratio, 2.96; 95% confidence interval, 1.92-4.58). A total of 139 (26.7%) participants requested the HBSST service online and 43.2% (60/139) returned the specimen for testing, in which 2 positives (3.3%) were found. CONCLUSIONS: The knowledge on CT and the previous uptake or current willingness to have a testing for CT was low among Chinese young students.

Treatment of maternal syphilis for preventing congenital syphilis: an observational study of adherence to treatment recommendation in Suzhou, China, 2019-2021.

BACKGROUND: China is one of the countries that set the goal to eliminate mother-to-child transmission (EMTCT) of syphilis by a target date. Active screening for syphilis among pregnant women, followed by effective treatment of maternal syphilis, is critical for achieving the goal. The China health authority issued national implementation protocols to guide EMTCT practice in health facilities. METHODS: Within a cohort of infants born to mothers infected with syphilis, we obtained the data of regimens used for treatment of maternal syphilis from the National Information System of Prevention of Mother-to-Child Transmission of HIV, Syphilis and Hepatitis B, and analysed the physician's treatment behaviour and its associated factors in a public hospital in Suzhou of China. RESULTS: A total of 450 pregnant women who were positive for treponemal or non-treponemal antibody, or had previous infection with syphilis were included into the study for analysis. Of them, 260 (57.8%) were positive for both treponemal and non-treponemal antibodies (syphilis seropositivity), and 353 (78.4%) were treated for syphilis according to the protocol in which 123 (34.8%) were treated with two courses. Non-adherence to treatment recommended by the protocol for maternal syphilis was significantly associated with antenatal visits in the third trimester (AOR 6.65, 95% CI 2.20-20.07, P =0.001), being positive only for a treponemal test (AOR 5.34, 95% CI 3.07-9.29, P <0.001) or having a syphilis infection before the pregnancy (AOR 2.05, 95% CI 1.14-3.69, P =0.017), whereas the uptake of treatment for two treatment courses was associated with attending antenatal care in 2020 or before (AOR 3.49, 95% CI 1.89-6.42, P <0.001), being positive for treponemal and non-treponemal tests (AOR 5.28, 95% CI 2.78-10.06, P <0.001) or having non-treponemal antibody titre of ≥1:8 (AOR 3.71, 95% CI 1.77-7.78, P =0.001). CONCLUSIONS: Implementation of the current recommendation to offer a universal treatment for syphilis among all pregnant women who are shown to be positive for a treponemal test alone is challenging in some clinical settings in China.

Developmental characteristics of visual evoked potentials to different stimulation in normal children.

OBJECTIVE: To determine the developmental characteristics of flash visual evoked potentials (FVEP) and pattern-reversal visual evoked potentials (PVEP) of healthy children. METHODS: The data were collected with a Keypoint Workstation 9033A07; 168 children (2 months-13 years) were tested with FVEP and 101 (4-13 years) were tested with PVEP. RESULTS: A triphasic waveform with clear components (N2, P2, and N3) was recorded steadily after 1 year, with occurrence rates over 97% at all frequencies. FVEP latency significantly decreased with age. The amplitude difference of FVEP was greater for binocular than monocular fields. FVEP amplitude increased and amplitude differences decreased with stimulation frequency. The occurrence rate of PVEP was 100% after 4 years, and PVEP latency was significantly prolonged with age. N75 and P100 amplitudes and the N75-P100 amplitude difference increased with field of vision. CONCLUSION: FVEP can be evoked in normal children at less than 2 Hz. Stimulation frequency can be adjusted to improve early detection and verification of subclinical lesions. The PVEP waveform is simple and stable, and its results are easier to analyze and interpret than FVEP, but it is limited by visual acuity and fixation force, whereas FVEP is affected less by visual acuity. but it is necessary to establish normal reference values of each age in each laboratory because of complicated analysis. According to the specific situation of the patient (vision, fixation) and clinical demand, we need to choose the right stimulation.

Curcumin attenuates intracerebral hemorrhage-induced neuronal apoptosis and neuroinflammation by suppressing JAK1/STAT1 pathway.

Intracerebral hemorrhage (ICH) is a kind of fatal stroke with the highest mortality and morbidity in the world. To date, there is no effective treatment strategy for ICH. Curcumin, a major active ingredient of Curcuma longa L., possesses a potential anti-inflammatory activity in many types of disease. In the current study, the mechanism underlying curcumin attenuated ICH-induced neuronal apoptosis and neuroinflammation was explored. Herein, we studied that curcumin decreased brain edema and improved neurological function by using brain edema measurement, assessment of neurological-deficient score, immunofluorescence, and Western blotting analyses after ICH. The results showed that curcumin improved ICH-induced neuronal apoptosis and neuroinflammation. Functionally, the polarization of microglia was assessed by immunofluorescence and Western blotting analyses after ICH in the absence or presence of curcumin. The results suggested that the M1-type microglia were activated after ICH, while the effect was blocked by curcumin treatment, suggesting that curcumin alleviates the neuroinflammation and apoptosis of neurons by suppressing the M1-type polarization of microglia. Mechanically, M1 polarization of microglia was regulated by JAK1/STAT1, and the activation of JAK1/STAT1 was blocked by curcumin. Meanwhile, the protective function of curcumin can be blocked by RO8191, an activator of JAK1. Taken together, our study suggested that curcumin improved the ICH-induced brain injury through alleviating M1 polarization of microglia/macrophage and neuroinflammation via suppressing the JAK1/STAT1 pathway.

[A Rare Case of Extremely High Counts of EpCAM + Circulating Tumor Cells and Circulating Tumor Microemboli Detected in a Patient with Small Cell Lung Cancer].

A 77-year-old man was admitted at our hospital due to "generalized increase in the number of masses and enlargement of the masses observed for one month". Combined assessment of the imaging (computed tomography and magnetic resonance imaging) findings and results of lung centesis biopsy and liquid biopsy suggest that the patient had small cell lung cancer of the left upper lobe, with right hilar, mediastinal, bilateral axillary, abdominal and retroperitoneal lymph node metastases, as well as widespread subcutaneous soft tissue, liver, bilateral adrenal, bilateral kidneys and multiple brain metastases (extensive stage). In order to obtain an evaluation of the development of the disease as soon as possible, the circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) in 6 mL peripheral blood were examined by subtraction enrichment-immunostaining fluorescence in situ hybridization (SE-iFISH) technology. A total of 919 epithelial cell adhesion molecule (EpCAM)-positive CTCs and 61 EpCAM-positive CTM were identified. Among them, there were 14 haploid CTCs (1.52%), 788 diploid CTCs (85.75%), 44 triploid CTCs (4.79%), 70 tetraploid CTCs (7.62%) and 3 pentaploid or higher-fold polyploid CTCs (0.33%). Herein, we reported a rare case with extremely high accounts of CTCs and CTM and positive findings for tumor markers, which was identified for the first time. The examination of CTCs by SE-iFISH contributed to the diagnosis, prognosis and treatment evaluation of cancer and facilitated the formulation of precise and individualized therapeutic regime.

Application of SifaInDel 45plex System in the Han and Mongolian Populations.

OBJECTIVES: To investigate the genetic polymorphism of InDel loci in SifalnDel 45plex system in the Han population in Jiangsu Province and the Mongolian population in Inner Mongolia, and to evaluate the effectiveness of the system in forensic medicine. METHODS: SifaInDel 45plex system was used for genotyping in blood samples of 398 unrelated individuals from the above two populations, and allele frequencies and population genetic parameters of the two populations were calculated respectively. Eight intercontinental populations in the gnomAD database were used as reference populations. The genetic distances between the two studied populations and eight reference populations were calculated based on the allele frequencies of 27 autosomal-InDels (A-InDels). The phylogenetic trees and multidimensional scaling (MDS) analysis diagrams were constructed accordingly. RESULTS: Among two studied populations, the 27 A-InDels and 16 X-InDels showed no linkage disequilibrium between each other and the allele frequency distributions were in Hardy-Weinberg equilibrium. The CDP of the 27 A-InDels in two studied populations were all higher than 0.999 999 999 9, and the CPEtrio were all less than 0.999 9. The CDP of the 16 X-InDels in Han in Jiangsu and Mongolian in Inner Mongolia female and male samples were 0.999 997 962, 0.999 998 389, and 0.999 818 940, 0.999 856 063, respectively. The CMECtrio were all less than 0.999 9. The results of population genetics showed that the Jiangsu Han nationality, Inner Mongolia Mongolian nationality and East Asian population clustered into one branch, showing closer genetic relationship. The other 7 intercontinental populations clustered into another group. And the above 3 populations displayed distant genetic relationships with the other 7 intercontinental populations. CONCLUSIONS: The InDels in the SifaInDel 45plex system have good genetic polymorphism in the two studied populations, which can be used for forensic individual identification or as an effective complement for paternity identification, and to distinguish different intercontinental populations.

Oral Manifestations of Early Syphilis in Adults: A Systematic Review of Case Reports and Series.

ABSTRACT: Rapid emergence of syphilis and oral sexual behaviors has focused attention on oral syphilis, and published reports of cases with oral syphilis have increased in the recent decades. We performed a systematic literature review by searching articles from PubMed, EMBSE, and Google Scholar, looking for case reports or series that would potentially have the clinical characteristics and outcomes for each individual case with oral syphilis. A total of 145 cases with the infection, from 95 studies, were identified to include in our review. Two main clinical phenotypes (ulcerative lesions and mucous patches) appeared to be of particular relevance to oral manifestations. A solitary ulcer was mostly manifested as the lesion of primary syphilis (91.7%) preferentially located on the upper lip, tongue, palate, and buccal mucosa. The most affected anatomical site in the patients with single location involved was the tongue (37.5%), followed by the lips (29.5%), palates (19.3%), and buccal mucosa (6.8%). It is concluded that oral syphilis has its predominant clinical phenotypes although it can manifest in diverse manners.

Tetranorlanostane and Lanostane Triterpenoids with Cytotoxic Activity from the Epidermis of Poria cocos.

Two unprecedented tetranorlanostane triterpenoids, poricolides A (1) and B (2), and two new lanostane triterpenoids, 3ß-acetoxy-24-methyllanosta-8,16,24(31)-trien-21-oic acid (3) and 3ß-acetoxylanosta-7,9(11),16,23-tetraen-21-oic acid (4), were isolated from the epidermis of Poria cocos. The structures of 1-4 were determined via analysis of 1 H-, 13 C-, and 2D-NMR, and HR-ESI-MS data, and the absolute configurations of 1 and 3 were established by single-crystal X-ray diffraction analysis. Compounds 1 and 2 were the first report of tetranorlanostane triterpenoid having a δ-lactone ring at C(17). Compounds 3 and 4 were rare lanostane triterpenoids having a double bond between C(16) and C(17). Compounds 1-4 exhibited potent antiproliferative effects against A549, SMMC-7721, MCF-7, and SW480 cancer cell lines with IC50 values from 16.19±0.38 to 27.74±1.12 µM.

Serum sCD14, PGLYRP2 and FGA as potential biomarkers for multidrug-resistant tuberculosis based on data-independent acquisition and targeted proteomics.

Multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis (TB) resistant to at least isoniazid and rifampicin, is a major concern of TB control worldwide. However, the diagnosis of MDR-TB remains a huge challenge to its prevention and control. To identify new diagnostic methods for MDR-TB, a mass spectrometry strategy of data-independent acquisition and parallel reaction monitoring was used to detect and validate differential serum proteins. The bioinformatic analysis showed that the functions of differential serum proteins between the MDR-TB group and the drug-sensitive tuberculosis group were significantly correlated to the complement coagulation cascade, surface adhesion and extracellular matrix receptor interaction, suggesting a disorder of coagulation in TB. Here, we identified three potential candidate biomarkers such as sCD14, PGLYRP2 and FGA, and established a diagnostic model using these three candidate biomarkers with a sensitivity of 81.2%, a specificity of 90% and the area under the curve value of 0.934 in receiver operation characteristics curve to diagnose MDR-TB. Our study has paved the way for a novel method to diagnose MDR-TB and may contribute to elucidate the mechanisms underlying MDR-TB.

Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis.

BACKGROUND: Plasmodium falciparum circumsporozoite protein (PfCSP) is a potential malaria vaccine candidate, but various polymorphisms of the pfcsp gene among global P. falciparum population become the major barrier to the effectiveness of vaccines. This study aimed to investigate the genetic polymorphisms and natural selection of pfcsp in Bioko and the comparison among global P. falciparum population. METHODS: From January 2011 to December 2018, 148 blood samples were collected from P. falciparum infected Bioko patients and 96 monoclonal sequences of them were successfully acquired and analysed with 2200 global pfcsp sequences mined from MalariaGEN Pf3k Database and NCBI. RESULTS: In Bioko, the N-terminus of pfcsp showed limited genetic variations and the numbers of repetitive sequences (NANP/NVDP) were mainly found as 40 (35%) and 41 (34%) in central region. Most polymorphic characters were found in Th2R/Th3R region, where natural selection (p > 0.05) and recombination occurred. The overall pattern of Bioko pfcsp gene had no obvious deviation from African mainland pfcsp (Fst = 0.00878, p < 0.05). The comparative analysis of Bioko and global pfcsp displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p < 0.05). The global pfcsp C-terminal sequences were clustered into 138 different haplotypes (H_1 to H_138). Only 3.35% of sequences matched 3D7 strain haplotype (H_1). CONCLUSIONS: The genetic polymorphism phenomena of pfcsp were found universal in Bioko and global isolates and the majority mutations located at T cell epitopes. Global genetic polymorphism and geographical characteristics were recommended to be considered for future improvement of malaria vaccine design.

Caesalpanins A-C, Three Dimeric Cassane Diterpenoids from the Seeds of Caesalpinia sappan L.

Three dimeric cassane diterpenoids, caesalpanins A-C, were isolated from the seeds of Caesalpinia sappan L., as well as three known compounds. Their structures were determined via analysis of 1D-, 2D-NMR, and HR-ESI-MS data. Caesalpanins A and B were the second and third compounds that presented a nitrogen-containing cassane diterpenoid dimer linked through one ether bond between C-19 and C-20'. Caesalpanin B exhibited moderate cytotoxic activity against MCF-7 cell lines with IC50 value of 29.98 µm. Caesalpanins A and B had weak inhibitory effects against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages at 50 µm with inhibitory rate of 36.01 % and 32.93 %, respectively.

The analgesic efficacy of ultrasound-guided transversus abdominis plane block for retroperitoneoscopic renal surgery: a randomized controlled study.

BACKGROUND: Ultrasound-guided lateral transversus abdominis plane (TAP) block can provide definite analgesia to the anterior abdominal wall. However, whether this method is useful in renal surgery through the lateral abdominal wall pathway remains unknown. The study aimed to evaluate the analgesic efficacy of lateral TAP block for retroperitoneoscopic partial or radical nephrectomy. METHOD: In this prospective, randomized, double-blind, placebo-controlled trial, eligible patients were randomized into two groups. After anaesthesia induction, ultrasound-guided lateral TAP block was performed with either 30 ml of 0.4% ropivacaine (Group T) or an equivalent volume of normal saline (Group C). The primary outcomes were opioid consumption during surgery and in the first 24 h after surgery. Secondary outcomes included postsurgical pain intensity immediately awakening from anaesthesia and at 0.5, 1, 2, 6, 12, and 24 h after surgery, as well as recovery variables including the incidence of postoperative nausea and vomiting (PONV), sleep quality, time to first ambulation, drainage and length of hospital stay. RESULTS: A total of 104 patients were enrolled and randomized (53 in Group T and 51 in Group C). Laparoscopic surgery was converted to open surgery in one patient of Group T; this patient was excluded from the outcome analysis. The opioid consumption during surgery (intravenous morphine equivalent dose: median 35.0 mg [interquartile range 18.0, 49.6] in Group C vs. 40.3 mg [20.9, 59.0] in Group T, P = 0.281) and in the first 24 h after surgery (10.8 mg [7.8, 21.7] in Group C vs. 13.2 mg [8.0, 26.6] in Group T, P = 0.311) did not differ significantly between groups. There were no significant differences between groups regarding the pain intensity at all time points after surgery and the recovery variables (all P > 0.05). CONCLUSIONS: Our results showed that, in patients undergoing retroperitoneoscopic renal surgery, preoperative lateral TAP did not decrease intra- and postoperative opioid consumption, nor did it relieve pain intensity or promote postoperative recovery in the first 24 h after surgery. However, the trial might be underpowered. TRIAL REGISTRATION: This study was registered on November 4, 2017, in the Chinese Clinical Trail Registry with the identification number ChiCTR-INR-17013244 .

Effects of gestational diabetes mellitus on time to delivery and pregnancy outcomes in full-term pregnancies with dinoprostone labor induction.

OBJECTIVE: To investigate the effects of gestational diabetes mellitus (GDM) on time to delivery and perinatal outcomes in full-term pregnancies underwent dinoprostone-induced labor. METHODS: GDM patients that underwent labor induction with dinoprostone vaginal inserts were retrospectively recruited. Full-term pregnancies with normal glucose tolerance (NGT) that underwent labor induction at the same period were recruited as control. Time to delivery and perinatal outcomes were compared between the two groups. RESULTS: A total of 1555 pregnancies with 226 GDM and 1329 NGT were recruited. GDM pregnancies had older ages, lower gestational age, higher body mass index (BMI) and abortion history, and more multigravida than NGT pregnancies (P< 0.05). Univariate analysis showed no significant difference in time to delivery and delivery rates between the two groups. However, after adjusted in a multivariate analysis model, the delivery rates of GDM women delivered within 12, 24, 36 or 48 h and those vaginally delivered within 12 or 36 h were significantly lower than those in the NGT group (P< 0.05). Perinatal outcomes were clinically similar between the two groups. CONCLUSION: GDM did not affect the time to delivery, cesarean delivery and other perinatal outcomes in Chinese women underwent dinoprostone-induced labor. However, it may be associated with the lower rates of delivery within different time intervals.

[Research advances in relationship between biological clock and cardiovascular diseases].

Circadian rhythms widely exist in living organisms, and they are regulated by the biological clock. Growing evidence has shown that circadian rhythms are tightly related to the physiological function of the cardiovascular system, including blood pressure, heart rate, metabolism of cardiomyocytes, function of endothelial cells, and vasoconstriction and vasodilation. In addition, disruption of circadian rhythms has been considered as one of the important risk factors for cardiovascular diseases, such as myocardial infarction. This review summarizes the recent research advances in the relationship between circadian clock and cardiovascular diseases, hoping to improve treatment strategies for patients with cardiovascular diseases according to the theory of biological clock.