Real-world treatment patterns and outcomes for patients with CLL using the Australian pharmaceutical benefits scheme (PBS) dataset.

This real-world retrospective cohort study using Australian Pharmaceutical Benefits Scheme (PBS) 10% investigated changes in chronic lymphocytic leukemia (CLL) treatment by line of therapy, time-to-next-treatment, treatment duration, and overall survival (OS). Overall, 803 patients received their first PBS-reimbursed CLL medication between 1 January 2011 to 31 July 2021 (median age: 70 years; 64.6% male), 289 post-1 August 2020. In 2011, most first-line (1 L) prescribing was fludarabine, cyclophosphamide, and rituximab (FCR). By 2021, common 1L were chlorambucil ± CD20 (26.1%), Bruton Tyrosine Kinase inhibitor (BTKi) (26.1%), and CD20 monotherapy (23.9%). In 2011, relapsed/refractory (R/R) CLL treatment was CD20 monotherapy or FCR. By 2021, BTKi (57.7%) and venetoclax ± CD20 (26.1%) were most common. Compared to FCR, 1 L treatment duration (Hazard Ratio) was shorter for CD20 monotherapy (1.7) or chlorambucil ± CD20 (2.5). In R/R CLL, median duration was 24 (ibrutinib) and 19 months (venetoclax). Median OS was 127 months. CLLtreatment pattern shave greatly changed in Australia since the introduction of novel therapies.

Clinical evaluation of droplet digital pcr for suspected ascites infection in patients with liver cirrhosis.

BACKGROUND: Droplet digital PCR (ddPCR) is increasingly used in diagnosing clinical pathogens, but its effectiveness in cirrhosis patients with suspected ascites infection remains uncertain. METHODS: The diagnostic performance of ddPCR was assessed in 305 ascites samples, utilizing culture and clinical composite standards. The quantitative value and potential clinical impact of ddPCR were further analyzed in patients with spontaneous bacterial peritonitis. RESULTS: With culture standards, ddPCR demonstrated a sensitivity of 86.5% and specificity of 83.2% for bacterial or fungal detection. After adjustment of clinical composite criteria, specificity increased to 96.4%. Better diagnostic performance for all types of targeted pathogens, particularly fungi, was observed with ddPCR compared to culture, and more polymicrobial infections were detected (30.4% versus 5.7%, p < 0.001). Pathogen loads detected by ddPCR correlated with white blood cell count in ascites and blood, as well as polymorphonuclear cell (PMN) count in ascites, reflecting infection status rapidly. A positive clinical impact of 55.8% (43/77) was observed for ddPCR, which was more significant among patients with PMN count ≤ 250/mm3 in terms of medication adjustment and new diagnosis. ddPCR results for fungal detection were confirmed by clinical symptoms and other microbiological tests, which could guide antifungal therapy and reduce the risk of short-term mortality. CONCLUSIONS: ddPCR, with appropriate panel design, has advantages in pathogen detection and clinical management of ascites infection, especially for patients with fungal and polymicrobial infections. Patients with atypical spontaneous bacterial peritonitis benefited more from ddPCR.

Clinical Evaluation of Metagenomic Next-Generation Sequencing Method for the Diagnosis of Suspected Ascitic Infection in Patients with Liver Cirrhosis in a Clinical Laboratory.

Metagenomic next-generation sequencing (mNGS), mostly carried out in independent clinical laboratories, has been increasingly applied in clinical pathogen diagnosis. We aimed to explore the feasibility of mNGS in clinical laboratories and analyze its potential in the diagnosis of infectious ascites. Two reference panels composed of 12 strains commonly appearing in peritonitis were constructed to evaluate the performance metrics based on in-house mNGS protocols. The mNGS clinical detection value was analyzed in 211 ascitic samples and compared with culture and composite standards. Finally, eight patients with cirrhosis were prospectively enrolled to verify the clinical value of mNGS in peritoneal infection diagnosis. The mNGS analytical performance showed that the assay had great linearity, specificity, stability, interference, and limits of detection of 33 to 828 CFU/mL. The sensitivity and specificity of mNGS for bacterial or fungal detection using culture standards were 84.2% and 82.0%, respectively. After adjustment using digital PCR and clinical judgment, the sensitivity and specificity increased to 87.2% and 90.1%, respectively. Compared with culture, mNGS detected a broad range of pathogens and more polymicrobial infections (49% versus 9%, P < 0.05). The pathogen results were obtained within 24 h using mNGS in eight prospective cases, which effectively guided antibiotics therapy. mNGS testing in clinical laboratories affiliated with a hospital has certain advantages. It has unique superiority in pathogens detection, particularly in patients with polymicrobial infections. However, considering spectrum characteristics and test cost, pertinent pathogen panels should be developed in clinical practice. IMPORTANCE This study established and evaluated a complete metagenomics next-generation sequencing assay to improve the diagnosis of suspected ascitic infection in a clinical laboratory affiliated with a hospital. The assay is superior to traditional culture testing and will aid in the early and accurate identification of pathogens, particularly in patients with polymicrobial infections. This assay is also essential for precision therapy and can reduce the incidence of drug resistance stemming from irrational use of antibiotics.

Patient Access to Orphan Drugs Covered by Medical Insurance in China: Real-World Evidence From Patient Survey.

BACKGROUND: After the inclusion of more high-cost orphan drugs in China's National Reimbursement Drugs List, this study investigated issues relating to patient access to the 7 medicines for 4 rare diseases after listing. METHODS: This study collected data from a national survey conducted in China. Three aspects associated with the accessibility of medicines, namely, approachability, availability, and affordability, were analyzed using descriptive statistics. In addition, multilevel logistic regression models were used to investigate the associations between patient characteristics and the accessibility of surveyed orphan drugs. RESULTS: Of the 999 completed responses included in the study, 15% of the patients (n = 150) did not use the medicines because of non-medicine-related issues. Among the 849 patients using the surveyed medications, 64.4% (n = 547) encountered the problem of unavailability, whereas 51.2% (n = 435) reported affordability as an issue, and 49.6% (n = 320) had health expenditure beyond the catastrophic threshold. The data also indicated that Commercial Medical Insurance helped patients to relieve the cost burden on orphan drugs, but the payout of Commercial Medical Insurance failed to influence patients' decisions to continue the treatments. CONCLUSION: Accessibility of orphan drugs has improved in China after their inclusion in the National Reimbursement Drugs List. Nevertheless, the availability and affordability of medicines remained the barriers for patients to access the desired treatments. It is recommended that further policy refinement in conjunction with the collaboration among healthcare stakeholders is required to deliver better care for patients with rare disease.

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy.

BACKGROUND: High-dose methotrexate (HD-MTX) combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL); however, some patients have adverse reactions. AIM: To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen. METHODS: Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HD-MTX until disease progression, intolerable toxicities, or physician/patient-directed withdrawal. Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria, respectively. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression-free survival, overall survival (OS), and safety. RESULTS: The median follow-up duration was 14.7 mo (range, 3.9-30 mo). The ORR for all patients was 84.2%, and 2-year progression-free- and OS rates were 75.6% and 94.1%, respectively. All patients completed the induction phase, and nine patients underwent autologous stem cell transplantation as consolidation therapy, resulting in an ORR of 88.9%. Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%. All patients showed an acceptable safety profile. The sequencing results for cerebrospinal fluid (CSF) and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations. Circulating tumor DNA was correlated with disease relapse and response. CONCLUSION: Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients. Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Psychometric Evaluation of the Mandarin HeartQoL Health-Related Quality of Life Questionnaire Among Patients With Ischemic Heart Disease in China.

OBJECTIVES: This study evaluated the psychometric properties of the Mandarin version of the HeartQoL questionnaire, a core ischemic heart disease (IHD) health-related quality of life (HRQL) instrument, in patients with angina, myocardial infarction (MI), and ischemic heart failure (IHF). METHODS: The English version of HeartQoL was translated into Mandarin. A cross-sectional study was then conducted in mainland China using the Mandarin HeartQoL, Short Form-12 Health Survey, and Hospital Anxiety and Depression Scale. Factor analysis was used to establish the HeartQoL structure and internal consistency reliability and construct validity were assessed. RESULTS: Patients with IHD (n = 412; angina = 112, MI = 151, and IHF = 149) were enrolled. Significantly higher HeartQoL HRQL scores were reported by patients with either angina or MI than by patients with IHF. The 2-factor structure was confirmed by Mokken scale analysis in the total group with strong H coefficients on the global scale (0.64) and both the physical (0.70) and emotional (0.80) subscales. Internal consistency reliability was strong with Cronbach's α ranging from 0.90 to 0.95. Convergent validity was confirmed with strong correlations between similar physical and mental HeartQoL and Short Form-12 Health Survey subscales ranging from 0.77 to 0.82 with divergent validity confirmed with significantly lower correlations between dissimilar constructs. Discriminative validity was confirmed for 72% of the a priori sociodemographic and clinical hypotheses. CONCLUSIONS: The Mandarin version of the HeartQoL HRQL questionnaire demonstrates acceptable internal consistency reliability and convergent, divergent, and discriminative validity in patients with IHD and in each diagnostic subgroup. The data support the use of the HeartQoL to assess and compare HRQL in Mandarin-speaking patients with IHD.

V-Y latissimus dorsi musculocutaneous flap for reconstruction of chest wall defects after local advanced breast cancer surgery: Report of 14 cases / 中华显微外科杂志

Objective:To demonstrate the clinical effect of latissimus dorsi musculocutaneous flap with primary closure in V-Y suture in the repair of major lesions in the anterior chest wall that was left after mastectomies with locally advanced breast cancer (LABC) surgery.Methods:From September 2018 to February 2021, the technique was employed on 14 female cancer patients who had LABC surgery in the Department of Breast Surgery of the First Affiliated Hospital of Kunming Medical University. The patients received radical mastectomies with major resection of cutaneous tegument. The defect areas in chest wall were 15.0 cm×15.0 cm-22.0 cm×35.0 cm. The sizes of flap were 12.0 cm×28.0 cm-18.0 cm×35.0 cm. The sizes of musculocutaneous flap were 12.0 cm×28.0 cm×2.0 cm~18.0 cm×35.0 cm×3.5 cm. All patients were entered the postoperative follow-up through out-patient clinic and telephone interviews.Results:The flap provided an efficient coverage in closing the defects among all 14 patients. Three patients presented small areas (1.0-3.0 cm) of superficial necrosis in Y-cross area of the flap. None of the patient had back swelling. The average operation time was 6.3 hours. Postoperative follow-up varied from 4 to 41 months(18 months in average). The colour, texture, elasticity of the flaps were acceptable, with good shapes. Function of upper limbs was normal in 13 cases without lymphedema, except 1 who had lymphedema of affected limb at 3 years after surgery. Eleven cases had radiotherapy after surgery with good tolerance. None of the cases had local recurrence of breast cancer. Five cases had metastasis, 3 cases died of metastasis.Conclusion:The latissimus dorsi musculocutaneous flap with primary closure in V-Y suture is easy to perform and an reliable and efficient technique in repairing large defects in the anterior chest wall left after a LABC surgery.

Primary cardiac lymphoma: the management and outcome of a single-centre cohort of 22 patients.

BACKGROUND: The incidence of primary cardiac lymphoma (PCL) is increasing, but the optimal management approach remains unclear. We assessed the clinical characteristics of a single-centre cohort with the goal of determining the optimal management approach. The treatment outcomes and prognostic factors are reported. MATERIAL AND METHODS: All PCL patients were diagnosed via biopsy guided by whole-body imaging (positron emission tomography/computed tomography [PET/CT] and/or contrast-enhanced CT]. Curative therapy involved either surgery or prephase steroids followed by definitive immunochemotherapy, depending on the histological type. The primary outcomes were overall survival (OS) and progression-free survival (PFS); the secondary outcome was the treatment response. RESULTS: Twenty-two PCL patients (14 males, 8 females; age: 59.5 ± 14.7 years [mean ± S.D.]) were histologically confirmed to have diffuse large B-cell lymphoma (DLBCL; n = 17 [77.3%]), fibrin-associated DLBCL (FA-DLBCL) (n = 4 [18.2%]) and Burkitt lymphoma (n = 1 [4.5%]). Seven patients underwent cardiotomy (three for biopsy, four with curative intent). The median and longest follow-up periods were 16.3 and 180.0 months, respectively. The 16 patients who received curative therapy (complete response [CR], n = 15 [93.8%]; partial response [PR], n = 1 [6.2%]) showed better survival than those who did not (5-year OS: 83.0 ± 11.3% vs. 0%; hazard ratio [HR]: 0.025[95% confidence interval, CI: 0.003-0.187], p < 0.001); 5-year PFS: 78.7 ± 11.0% vs. 0%, HR= 0.010[0.001-0.093], p < 0.001). The left ventricular ejection fractions (LVEF) before and after definitive treatment was 63.6 ± 2.4% and 64.6 ± 4.5%, respectively (p = 0.275, power = 0.318). Extrapericardial lesions were associated with poorer survival (5-year OS: 40.0 ± 29.7% vs. 100%, p = 0.027; 5-year PFS:40.0 ± 21.9% vs. 100%, p = 0.010). CONCLUSIONS: Whole-body imaging is essential for diagnosis and prognosis. Curative therapy provided reasonable outcomes and survival; extrapericardial lesions were associated with a poorer treatment response.

[Clinical Efficacy of High Dose Methotrexate, Temozolomide and Rituximab in the Treatment of Patients with Primary Central Nervous System Lymphoma].

OBJECTIVE: To investigate the clinical efficacy of high dose methotrexate (HD-MTX), temozolomide (TMZ), and rituximab (R) in the treatment of patients with primary central nervous system lymphoma (PCNSL). METHODS: Clinical data of patients with PCNSL diagnosed and treated in Guangdong Provincial People's Hospital from February 2010 to May 2017 were collected. First, patients were given 6-8 cycles of MTX (3.5 g/m2) for induction treatment, and then 12 cycles of TMZ (150 mg/m2) for maintenance treatment. The day before induction treatment, patients were given rituximab 375 mg/m2 according to their economic status. A retrospective cohort study was performed on patients receiving HD-MTX+TMZ or HD-MTX+TMZ+R to analyze the efficacy and survival. RESULTS: There were 42 patients enrolled in the study, 17 cases in HD-MTX+TMZ group and 25 cases in HD-MTX+TMZ+R group. The median PFS and OS times in HD-MTX+TMZ+R group were 56.7 months and N/A, respectively, while, 7.3 months and 34.7 months in HD-MTX+TMZ group, respectively. In addition, there was no significant difference in median survival between patients who received TMZ maintenance therapy and those who were only actively monitored. During the induction period, all the patients had grade 1-2 nausea and vomiting, while in the consolidation treatment period, no grade 3/4 toxicity was observed. CONCLUSION: The combination of HD-MTX+TMZ+R in the treatment of PCNSL patients shows a definite short-term effect, which can increase the survival rate of the patients. The side effects are mild, and the patients can generally tolerate.

Direct qualitative and quantitative determination methodology for massive screening of DON in wheat flour based on multi-molecular infrared spectroscopy (MM-IR) with 2T-2DCOS.

Deoxynivalenol (DON) contamination in wheat flour induces a number of adverse health effects to consumers and livestock, even at very low concentrations. Direct detection methods for massive screening of DON in wheat flour is still lacking. A new methodology integrating multi-molecular infrared spectroscopy (MM-IR) with two-trace two-dimensional correlation spectroscopy (2T-2DCOS) was developed for in-situ qualitative and quantitative determination of DON in wheat flour as a whole. Typical spectral variation of wheat flour samples with diverse concentration of DON were stepwise characterized by MM-IR and tiny spectral profile differences resulting from concentration variation of DON were visually disclosed by 2T-2DCOS. Based on the obtained key spectral features of DON, 180 of wheat flour samples with DON higher and lower than 1.00 mg/kg were undoubtedly classified by Principal Component Analysis (PCA) and Support Vector Machines (SVM) with an accuracy rate up to 100% (for Second derivative spectra consisted of selected bands, SD-SS). Furthermore, a robust quantitative prediction model was established based on partial least squares (PLS) of SD-SS (Rc: 0.998, RMSEC: 0.135; Rp: 0.968, RMSEP: 0.421), and its excellent predictive capacity of model was validated by both residual prediction deviation (RPD) value of 3.2 and t-test. It was demonstrated that the developed methodology was applicable for screening and quantitative detection of DON in wheat flour based on the novel correlation analysis methods (SD-2DCOS-IR and 2T-2DCOS-IR) with chemometrics tools, which could be utilized both at laboratory and industrial level for quality control purposes of a large wheat flour sample set.

[Identify the Nitrate Sources in Different Land Use Areas Based on Multiple Isotopes].

Different land uses have different impacts on the water quality of the region. Multiple isotopes (δD-H2O, δ18O-H2O, δ15N-NO3-, and δ18O-NO3-) and the SIAR (stable isotope analysis in R) model were applied to identify the nitrate sources and estimate the proportional contributions of multiple nitrate sources in a river in a typical urban area (the Grand Canal, Hangzhou) and a river in a typical forest and agricultural area (Yuying Riveri). The results indicated that there were different degrees of nitrogen pollution in the Grand Canal and Yuying River; NO3--N and NH4+-N are the predominant forms of nitrogen in the Grand Canal, and the primary form of nitrogen in Yuying River was NO3--N. There was an obvious linear relationship between the hydrogen and oxygen isotopes (R2=0.78). The δD-H2O and δ18O-H2O values for the Grand Canal and Yuying River were distributed along the local meteoric waterline, indicating that precipitation served as the primary water source in these rivers. All of the δ18O-NO3- values of the Grand Canal and Yuying River were lower than 15 ‰. It was revealed that nitrification, rather than denitrification, was the primary N cycling process in the two rivers. The δ15N-NO3-/δ18O-NO3- ratios of some of the samples from the Grand Canal ranged from 1.3 to 2.1, accompanied by low concentrations of DO and NO2-, indicating that denitrification existed in some sections of the Grand Canal. The δ15N-NO3- values of the samples from the Grand Canal (average:6.1‰) were higher than those from the Yuying River (average:2.3‰). The NO3- source contributions differed significantly between the Grand Canal and Yuying River. The contributions of NO3- sources in the Grand Canal were sewage/manure (37.0%) > soil nitrogen (35.7%) > chemical fertilizer (19.1%) > precipitation (8.2%), and those in the Yuying River were chemical fertilizer (46.1%) > soil nitrogen (22.8%) > precipitation (17.3%) > sewage/manure (13.8%). The contribution of the sewage/manure was substantially increased in the Grand Canal in the urban area with stronger human activities primarily due to the sporadic discharge of domestic sewage and urban runoff. Chemical fertilizer is the main NO3- source in the Yuying River near the forest and agricultural area, suggesting that the nitrogen pollution caused by agricultural non-point sources was extremely serious. The contribution of precipitation decreased in the areas of substantial human activities. The isotopic fractionation produced by denitrification was affected by the contributions of the NO3- sources, which were calculated by SIAR model. Sewage/manure and chemical fertilizer produced significant impacts, followed by soil nitrogen and precipitation.

Discrepancies between proxy estimates and patient reported, health related, quality of life: minding the gap between patient and clinician perceptions in heart failure.

PURPOSE: Health related quality of life (HRQoL) is rarely routinely measured in the clinical setting. In the absence of patient reported data, clinicians rely on proxy and informal estimates to support clinical decisions. This study compares clinician estimates (proxy) with patient reported HRQoL in patients with advanced heart failure and examines factors influencing discrepancies. METHODS: Seventy-five patients with heart failure, (22 females, 53 males) completed the EQ-5D-5L questionnaire. Thirty-nine clinicians (11 medical, 23 nursing, 5 allied health) completed the proxy version (V1) producing 194 dyads. Correlation was assessed using Spearman's rank tests, systematic bias was examined with Bland-Altman analyses. Inter-rater agreement at the domain level, was investigated using linear weighted Kappa statistics while factors influencing the IRG were explored using independent student t-tests, analysis of variance and regression. RESULTS: There was a moderate positive correlation between clinician HRQoL estimates and patient reported utility (r = 0.38; p < .0005). Mean clinician estimates were higher than patient reported utility (0.60 vs 0.54; p = 0.008), with significant underestimation of reported problems apparent in three of the five EQ-5D-5L domains. Patient sex (female), depressed mood and frailty were all associated with an increased inter-rater gap. CONCLUSION: Clinicians in this sample overestimated HRQoL. Factors affecting the inter-rater gap, including sex and depression, support formal HRQoL screening to enhance clinical conversations and decision making. The discrepancy also supports regulatory restriction on the use of expert opinion in the development of QALYs in health economic analysis.

Clinical Efficacy of High Dose Methotrexate, Temozolomide and Rituximab in the Treatment of Patients with Primary Central Nervous System Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical efficacy of high dose methotrexate (HD-MTX), temozolomide (TMZ), and rituximab (R) in the treatment of patients with primary central nervous system lymphoma (PCNSL).@*METHODS@#Clinical data of patients with PCNSL diagnosed and treated in Guangdong Provincial People's Hospital from February 2010 to May 2017 were collected. First, patients were given 6-8 cycles of MTX (3.5 g/m@*RESULTS@#There were 42 patients enrolled in the study, 17 cases in HD-MTX+TMZ group and 25 cases in HD-MTX+TMZ+R group. The median PFS and OS times in HD-MTX+TMZ+R group were 56.7 months and N/A, respectively, while, 7.3 months and 34.7 months in HD-MTX+TMZ group, respectively. In addition, there was no significant difference in median survival between patients who received TMZ maintenance therapy and those who were only actively monitored. During the induction period, all the patients had grade 1-2 nausea and vomiting, while in the consolidation treatment period, no grade 3/4 toxicity was observed.@*CONCLUSION@#The combination of HD-MTX+TMZ+R in the treatment of PCNSL patients shows a definite short-term effect, which can increase the survival rate of the patients. The side effects are mild, and the patients can generally tolerate.

EDTA-enhanced phytoremediation of heavy metals from sludge soil by Italian ryegrass (Lolium perenne L.).

Landscaping of sludge is a kind of recycling disposal, but the potential heavy metal risks limit its application. In this paper, the sludge soil was remediated by ryegrass, and the effect of ethylene diamine tetraacetic acid (EDTA) was studied through pot experiments. Italian ryegrass was planted in the sludge soil treated with six gradients concentrations of 0, 1, 2, 3, 4, 5 mmol kg-1 of EDTA, and the planting conditions were kept the same. After 45 days of planting, compared with the control group (without EDTA treated), the application of 1-5 mmol kg-1 EDTA decreased ryegrass biomass by 2-43%, reduced soil pH value by 0.21-0.34 unit, and reduced 4.1-9.7% capacity of exchange cation, but increased 1.4-8.6% soil organic matter. After growing ryegrass, the contents of heavy metals decreased by 10% for Cu, 15% for Zn, 6% for Ni, 14% for Cd and 44% for Pb; and after spraying EDTA decreased again by 33% for Cu, 31% for Zn, 56% for Ni, 24% for Cd, and 68% for Pb. In ryegrass, the uptake heavy metals were enhanced, and bio-concentration factor of Cu, Zn, Ni, Cd, and Pb of EDTA treated groups were 1.9, 1.6, 4.1, 2.7, and 4.8 times of the control group, respectively. However, EDTA only significantly increased transfer factor values of Cu and Zn, and made bio-extraction factor value of Cu greater than 1. The remediation factor values were used to comprehensive assess accumulation capacity of heavy metals by ryegrass under EDTA treating, and they ordered in Zn > Cu > Ni > Cd > Pb, and the best dose was 2 mmol kg-1 EDTA. Prediction models for bio-concentration factor were established by using stepwise multiple linear regression, explaining 94.9-99.3% of the corresponding elements with soil organic matter, EDTA dosage, and/or pH value (p < 0.005). This paper provided effective heavy metals remediation data for municipal sludge landscape and the prediction models.

Gut Microbiota Reconstruction Following Host Infection with Blood-stage Plasmodium berghei ANKA Strain in a Murine Model.

Malaria remains a global health problem. The relationship between Plasmodium spp. and the gut microbiota as well as the impact of Plasmodium spp. on the gut microbiota in vertebrate hosts is unclear. The aim of the current study was to evaluate the effect of blood-stage Plasmodium parasites on the gut microbiota of mice. The gut microbiota was analyzed by 16S rRNA sequencing and bioinformatic analyses at three stages. The gut microbiota changed during the three phases: the healthy stage, the infection stage, and the cure stage (on the 9th day after malarial elimination). Moreover, the gut microbiota of these infected animals did not recover after malaria infection. There were 254 operational taxonomic units (OTUs) across all three stages, and there were unique strains or OTUs at each stage of the experiment. The percentages of community abundance of 8 OTUs changed significantly (P<0.05). The dominant OTU in both the healthy mice and the mice with malaria was OTU265, while that in the cured mice was OTU234. In addition, the changes in OTU147 were the most noteworthy. Its percentage of community abundance varied greatly, with higher values during malaria than before malaria infection and after malaria elimination. These results indicated that the external environment influenced the gut microbiota after host C57BL/6 mice were infected with blood-stage P. berghei ANKA and that the same was true during and after elimination of blood-stage P. berghei ANKA. In addition, we could not isolate OTU147 for further study. This study identified gut microbiota components that were reconstructed after infection by and elimination of blood-stage P. berghei ANKA in host C57BL/6 mice, and this process was affected by P. berghei ANKA and the external environment of the host.

Association between SLC2A9 Genetic Variants and Risk of Hyperuricemia in a Uygur Population.

EN: Summary]This study aimed to test the effects of five single nucleotide polymorphisms within SLC2A9 on uric acid level in a special ethnic population, the Uygurs in Xinjiang, China. According to our inclusion and exclusion criteria, Uygur adults from Xinjiang constituted the study population. There were 1053 Uygur adults with hyperuricemia and 1373 normal Uygur adults who served as controls. Five single nucleotide polymorphisms within SLC2A9 (rs938557, rs7679916, rs7349721, rs13101785, and rs13137343) were selected with the HapMap dataset and TaqMan assays. We found that, in normouricemia group, rs938557 was significantly correlated with uric acid (ß=11.39±3.74, P=0.0024) adjusting for age, gender and BMI; rs7679916 and rs13137343 were marginally associated with uric acid concentration (ß=5.77±3.09, P=0.0626; ß= 5.99±3.08, P=0.0520). In the hyperuricemia group, no SNP was found to possibly influence uric acid concentration. None of these SNPs showed significant association with hyperuricemia after controlling for age, gender and BMI. There were significant or marginal correlations between certain single nucleotide polymorphisms in the SLC2A9 region and uric acid concentration in Uygur normouricemia samples. In turn, some of these single nucleotide polymorphisms in SLC2A9 may increase the risk of hyperuricemia.

Complete plastome sequence of Lysimachia congestiflora Hemsl. a medicinal and ornamental species in Southern China.

Lysimachia congestiflora Hemsl. is a perennial herb of Primulaceae. It is mainly distributed in the provinces to the south of the Changjiang River and south of Shanxi, Gansu province and Taiwan. It is a plant that combines medicinal, ornamental, and economic values. To date no study has been carried out on the genome of L. congestiflora. Here, we report and characterize the complete plastid genome sequence of L. congestiflora in order to provide genomic resources useful for promoting its conservation. The complete chloroplast genome of L. congestiflora is 154,505 bp in length with a typical quadripartite structure, consisting of a large single-copy region (LSC, 84,606 bp), a single-copy region (SSC, 17,961 bp), and a pair of inverted repeats (IRs, 25,969 bp). There are 114 annotated genes, including 80 unique protein-coding genes, 4 unique ribosomal RNA genes, and 30 transfer RNA genes. To investigate the evolution status of L. congestiflora, as well as Primulaceae, we constructed a phylogenetic tree with L. congestiflora and other 11 species based on their complete chloroplast genomes. According to the phylogenetic topologies, L. congestiflora was closely related to L. coreana.

Complete plastome sequence of Rhodoleia championii Hook. f. (Hamamelidaceae).

The complete chloroplast genome of Rhodoleia championii (Hamamelidaceae) was firstly reported in this study. The complete chloroplast genome of R. championii is 159,115 bp in length with a typical quadripartite structure, consisting of a large single-copy region (LSC, 88,123 bp), a single-copy region (SSC, 18,131 bp) and a pair of inverted repeats (IRs, 26,420 bp). There are 114 genes annotated, including 80 unique protein-coding genes, 4 unique ribosomal RNA genes, and 30 transfer RNA genes. According to the phylogenetic tree of R. championii and the other 9 species, R. championii was closely related to Chunia bucklandioides.

[Contribution of Nitrogen Sources in Water Sources by Combining Nitrogen and Oxygen Isotopes and SIAR].

It is very important to identify nitrate sources in reservoirs that serve as high quality water sources to control its eutrophication. Stable isotopes (δ15 N and δ18O) and a Bayesian model (stable isotope analysis in R, SIAR) were applied to identify nitrate sources and estimate the proportional contributions of multiple nitrate sources in four reservoirs (Qingshan reservoir, Duihekou reservoir, Siling reservoir, and Lifan reservoir) that serve as sources of drinking water in the Hangjiahu area, one of the most densely populated and most quickly developing areas in East China. It was shown that nitrogen pollution, which was dominated by nitrate (NO3-), existed in the four reservoirs. Greater human activities caused more nitrogen pollution (average NO3- concentration 0.21 mmol ·L-1) in the Qingshan reservoir. A significant positive correlation (P<0.01) was observed between Cl- and NO3-. The analysis of the water in the Duihekou reservoir, Siling reservoir, and Lifan reservoir, with lower Cl- concentrations and higher NO3-/Cl- ratios, suggested that chemical fertilizer was the main source, while the analysis of the water in the Qingshan reservoir, with medium Cl- concentrations and NO3-/Cl- ratios, indicated a mixture of NO3- sources. The δ15 N ranged from 0.9‰ to 7.2‰, and the δ18O ranged from 2.8‰ to 14.1‰ in the four reservoirs. The δ18O values in more than 86% of the water samples were less than 10‰, and the δ15 N/δ18O values in 93% of the water samples were less than 1.3. It was identified that nitrification rather than denitrification acted as the primary N cycling process in the four reservoirs. SIAR was used to estimate the proportional contribution of five NO3- sources (industrial wastewater, sewage/manure, chemical fertilizer, soil nitrogen, and precipitation) in the Qingshan reservoir and of three NO3- sources (chemical fertilizer, soil nitrogen, and precipitation) in the Duihekou reservoir, Siling reservoir, and Lifan reservoir. The source apportionment results showed that chemical fertilizers and soil nitrogen were the dominant nitrate sources and their contributions were 75%-82%. It was revealed that nitrogen pollution in the water source reservoir caused by cropping non-point source pollution was very serious. Nitrate source contributions in Qingshan reservoir also included sewage/manure (25%), soil nitrogen (7%), and precipitation (6%), indicating that nitrogen pollution by sewage/manure should not be ignored in the higher human activity areas. The nitrate source in the Duihekou reservoir, Siling reservoir, and Lifan reservoir also included precipitation, with the nitrate contribution from precipitation at 21%, 24%, and 15%, respectively. It was suggested that precipitation contributed more nitrate to the water in areas with less human activity.

[Nitrate Source Identification and Nitrification-denitrification at the Sediment-water Interface].

Identifying nitrate sources and its transformation mechanisms are important for nitrate pollution control in surface water. The columnar core sediment samples in West Lake were taken in different seasons. The transformation of nitrogen at the sediment-water interface was studied using nitrogen and oxygen isotopes, stable isotope analysis in R (SIAR) and acetylene inhibition method in the West Lake, Hangzhou. The results showed that the concentration gradient of both NO3-and NH4+ existed at the sediment-water interface. NO3- concentrations decreased from bottom water to pore water and NO3- was accumulated in sediments. NH4+ concentrations increased from bottom water to pore water and NH4+ was released from sediments. Nitrate sources in bottom water where nitrification exited were sewage (manure), soil nitrogen, chemical fertilizer and precipitation. Sewage (manure) was the major nitrogen contributor (60.8%) in summer. Particularly high δ15 N values in pore water indicated that there was strong denitrification at the sediment-water interface in West Lake. The average nitrification rate and denitrification rate at the sediment-water interface were 2.85 mmol·(m2·d)-1 and 23.51 µmol·(m2·d)-1, respectively. The sediment-water interface played a role in nitrogen removal process in aquatic environment. Seasonal and spatial variations of nitrification rates and denitrification rates were found in this study. Temperature and dissolved oxygen were the main influential factors for the transformation of nitrogen at the sediment-water interface in West Lake.