Biosynthesis and Assembly Logic of Fungal Hybrid Terpenoid Natural Products.

In recent decades, fungi have emerged as significant sources of diverse hybrid terpenoid natural products, and their biosynthetic pathways are increasingly unveiled. This review mainly focuses on elucidating the various strategies underlying the biosynthesis and assembly logic of these compounds. These pathways combine terpenoid moieties with diverse building blocks including polyketides, nonribosomal peptides, amino acids, p-hydroxybenzoic acid, saccharides, and adenine, resulting in the formation of plenty of hybrid terpenoid natural products via C-O, C-C, or C-N bond linkages. Subsequent tailoring steps, such as oxidation, cyclization, and rearrangement, further enhance the biological diversity and structural complexity of these hybrid terpenoid natural products. Understanding these biosynthetic mechanisms holds promise for the discovery of novel hybrid terpenoid natural products from fungi, which will promote the development of potential drug candidates in the future.

Glucocorticoid reduction induced chorea in pediatric-onset systemic lupus erythematosus: A case report.

BACKGROUND: Pediatric-onset systemic lupus erythematosus (SLE) is typically more severe than adult-onset SLE, with a higher incidence of nervous system involvement. Chorea is a relatively rare neurological complication reported in 2.4%-7% of SLE patients. In particular, chorea induced by glucocorticoid dose reduction is even rarer. Herein, we report the case of a girl with SLE, who developed chorea during the process of glucocorticoid therapy reduction. CASE SUMMARY: We describe a 14-year-old girl who was diagnosed with SLE. She was treated with methylprednisolone and rituximab, and her symptoms improved. On the second day after the methylprednisolone dose was reduced according to the treatment guidelines, the patient developed chorea. Her condition improved after adjusting her glucocorticoid regimen. CONCLUSION: This case is a reminder that extra attention to chorea is required in SLE patients during glucocorticoid dose reduction.

Myelodysplastic syndrome-like response after voriconazole treatment of systemic lupus erythematosus complicated with fungal infection: a case report.

Background: Voriconazole is mainly used to treat progressive and potentially life-threatening infections in immunocompromised patients. The adverse drug reactions related to voriconazole are varied. In some rare cases, the use of voriconazole can result in myelodysplastic syndrome (MDS)-like adverse reactions. Case presentation: Here, we present a rare case of systemic lupus erythematosus patient with a fungal infection that developed MDS-like adverse reactions after treatment with voriconazole. The patient was admitted to the hospital because of 3 days of chest tightness and dyspnea. After the admission, the patient's sputum culture showed Candida albicans infection, and voriconazole was prescribed to be taken orally. After using voriconazole, drug-related adverse reactions such as visual impairment, nausea, vomiting, hiccup, middle and lower abdominal pain, disorders of consciousness, delirium, hallucination, slow response, and subcutaneous ecchymosis appeared, as well as the gradually increased serum creatinine, oliguria, and aggravated lower limb edema. In addition, there was a decrease in peripheral blood cells, and MDS-like changes in bone marrow were indicated by bone marrow biopsy. After discontinuing voriconazole, drug-related adverse symptoms disappeared, and hematocytopenia and the changes in MDS were significantly improved, which was confirmed by a subsequent bone marrow puncture at a 6 months interval. Conclusion: This case reminded us that when using voriconazole for treatment, individual differences in patients should be considered, and the blood concentration of voriconazole should be closely monitored. Otherwise, potential drugs that affect voriconazole metabolism should be noted, and related adverse symptoms of patients should be closely observed during medication to reduce the occurrence of adverse drug events.

Molecular structure and evolution characteristics of dissolved organic matter in groundwater near landfill: Implications of the identification of leachate leakage.

Landfills can cause groundwater contamination, the pollution characteristics in groundwater near landfill sites have been extensively investigated, while the rapid identification of leachate leakage remained unclear. Comprehensively characterizing dissolved organic matter (DOM) is crucial for tracing the source, species, and migration of contaminants within groundwater and protecting groundwater sources. Here, we showed that DOM composition from newer landfills was mainly composed of newly-produced tryptophan and tyrosine, and protein-like and humic-like substances were more abundant in landfills that were relatively older. DOM in landfill groundwater was initially dominated by outputs from microbial activities, followed by terrigenous input. Leaked leachate contained an additional dye-derived fluorescent matter at the excitation/emission wavelength of 240-260/440-460 nm that was absent in uncontaminated groundwater. Leachate leakage increased the concentrations of humic-like substance, DOM molecular weight, and microbial activity in the downstream groundwater, resulting in the microorganisms rapidly multiply and secrete large amounts of microbial metabolism by-products, making them suitable indicators of groundwater pollution. Three criteria were proposed to establish an interpretable fluorescence method to identify leachate pollution. The obtained results provide a novel insight into not only the monitoring, early warning, and identification but also the transport, fate and removal or transformation of groundwater leachate in landfills.

[Polycyclic Aromatic Hydrocarbons in Surface Soil of China (2000-2020): Temporal and Spatial Distribution, Influencing Factors].

With the rapid development of China's economy and society, the polycyclic aromatic hydrocarbon (PAH) pollution of surface soil has attracted increasing attention. Based on a systematic review, this study identified 166 relevant papers (published from 2000 to 2020) dealing with the contamination of 16 PAHs in the surface soil of China and summarized the pollution level, temporal, and spatial distribution influencing factors of PAHs with statistics, spatial interpolation analysis, and source analysis methods. The results showed that the surface soil of China has been polluted by human-caused PAHs, with a median concentration of 675.70 µg·kg-1. Although the overall condition is good, some sampling points have been seriously polluted. Among the monomers of PAHs, the concentrations of fluoranthene (Fla) and pyrene (Pyr) are high, while acenaphthylene (Acy) and acenaphthene (Ace) are relatively low. During the survey period, the concentration data of surface soil PAHs are generally within the moderate pollution levels of 313.10-1070.45 µg·kg-1, while the annual changes of PAHs do not show obvious fluctuations and are less affected by oil production and consumption. Statistics and spatial interpolation results show that PAH pollution in the surface soil of China has regional characteristics, where the concentration decreases in order from northwest, north, east, northeast, southwest, and south-central China. The pollution level in most provinces is "contaminated" or "weakly contaminated." From the source analysis results, PAH pollution in surface soils in most areas of China comes from the high-temperature combustion of fossil fuels such as petroleum, biomass, and coal. Heilongjiang and some northwestern regions (e.g., Xinjiang and Tibet) were mainly represented by oil source pollution. Such results could provide a reference for soil environmental management and PAH pollution control in China.

Ginsenoside regulates Treg/Th17 cell ratio and inhibits inflammation to treat COPD.

Objective: Several studies have suggested an involvement of the immune system in the occurrence and development of chronic obstructive pulmonary disease (COPD), but the mechanism is still unclear. The aim of this study was to explore the mechanism of ginsenoside in inhibiting inflammation by regulating FOXP3 in COPD. Methods: Eighty COPD patients were selected and 35 healthy people were enrolled in the study to determine clinical efficacy, observation index, and SGRQ scores. Percentage of Treg and Th17 cells were detected by flow cytometry; HE staining was used to detect the effect of ginsenoside therapy on pathological changes of COPD in mice. Additionally, we transfected FOXP3 inhibitor; RT-PCR and western blot were used to detect the inflammation related genes and proteins. Results: The basic information of the patients were comparable. The clinical outcome in the treatment group was better than that in the control group, which indicated that ginsenoside has a certain therapeutic effect on COPD patients. The lung function and 6MWT distance results indicated that ginsenoside could stabilize the clinical symptoms of COPD patients and improve their quality of life. Flow cytometry results showed that ginsenoside can increase Treg expression while reducing Th17 cell expression. RT-PCR and western blot results showed that the expression of TNF-α and IL-17 in the model group was significantly increased after treatment, obviously caused by an increased expression of FOXP3. Conclusion: Ginsenoside can inhibit inflammation in COPD by up-regulating FOXP3.

[Prognostic Analysis of Primary Central Nervous System Lymphoma Patients with Diffuse Large B-Cell Immunophenotype].

OBJECTIVE: To investigate the prognostic influencing factors of primary central nervous system lymphoma (PCNSL) patients with diffuse large B-cell immunophenotype. METHODS: 42 PCNSL patients with diffuse large B-cell lymphoma treated in our hospital from March 2011 to October 2017 were enrolled. The effects of different treatments on overall survival of patients were analyzied. RESULTS: The analysis for 42 PCNSL patients with diffuse large B-cell immunophenotype showed that there was no affect of their clinical characteristics,such as sex, age, CSF protein content, treatment with and without temozolomide and rituximab on overall survival of the patients(P>0.05). And it was found that active treatment and the application of conventional intrathecal injection and methotrexate in the treatment could effectively prolong the overall survival time of patients. CONCLUSION: Early diagnosis of PCNSL and active standardized treatment can significantly prolong the survival time of patients, and it is further emphasized that the necessity of conventional intrathecal injection to prolong the survival of patients.

Association between interleukin 8-receptor gene (CXCR1 and CXCR2) polymorphisms and urinary tract infection: Evidence from 4097 subjects.

AIM: The aim of this study was to determine whether a correlation exists between interleukin-8 receptor polymorphisms and urinary tract infection (UTI) susceptibility. METHODS: We systematically searched electronic databases including PubMed, Embase, China National Knowledge Infrastructure, and Web of Science up to 5 November 2017 to select appropriate studies that focused on C-X-C chemokine receptor type 1 and/or 2 (CXCR1, CXCR2) polymorphisms with susceptibility to UTI. Eight case-control studies including 2085 patients with UTI and 2012 controls were enrolled in this study. Seven studies of CXCR1 rs2234671 and two studies of rs3138086 were included in the meta-analyses. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were synthesized using fixed-effects or random-effects model according to heterogeneity. RESULTS: No significant correlations were found between CXCR1 rs2234671 and rs3138086 polymorphisms and UTI susceptibility. However, subgroup analysis showed that rs2234671 was associated with an increased risk of UTI under allelic comparisons (C vs. G, OR = 1.95, 95% CI = 1.07-3.55), heterozygous model (GC vs. GG, OR = 1.93, 95% CI = 1.06-3.50), and dominant model (GC + CC vs. GG, OR = 1.98, 95% CI = 1.07-3.69) in children, especially in paediatric patients with acute pyelonephritis (allelic, OR = 2.43, 95% CI = 1.28-4.60; heterozygous, OR = 2.40, 95% CI = 1.24-4.62; dominant, OR = 2.48, 95% CI = 1.26-4.88). Furthermore, these results remained the same after eliminating paediatric patients with vesicoureteral reflux. CONCLUSION: CXCR1 rs2234671 polymorphism might be associated with an increased risk of UTI in children.

A PRISMA-compliant meta-analysis of MDR1 polymorphisms and idiopathic nephrotic syndrome: Susceptibility and steroid responsiveness.

BACKGROUND: Studies have investigated rs1128503, rs1045642, and rs2032582 in multidrug resistance protein 1 (MDR1) for association with susceptibility to idiopathic nephrotic syndrome (INS) and steroid resistance. However, because these findings were inconsistent, we performed a meta-analysis to determine whether there was evidence of a role of these MDR1 variants in INS. METHODS: The PubMed, Embase, and Web of Science databases were systematically searched to identify studies that examined MDR1 polymorphisms with susceptibility to INS and/or to steroid resistance. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model based on heterogeneity. RESULTS: We selected 9 case-control studies that included 928 patients with INS, of which steroid resistance data were available for 724 (236 were steroid resistant and 488 were steroid sensitive), and 879 healthy controls. All subjects were children. No significant relationships between these polymorphisms and INS susceptibility were identified. Significantly increased risk of steroid resistance was observed with rs1128503 allelic (OR = 1.49, 95% CI = 1.20-1.86) and genotypic (OR = 1.97, 95% CI = 1.18-3.30; OR = 2.03, 95% CI = 1.43-2.88) comparisons, and with allelic (OR = 1.56, 95% CI = 1.05-2.31) and genotypic (OR = 2.85, 95% CI = 1.15-7.07; OR = 2.21, 95% CI = 1.01-4.8) comparisons to rs2032582 in Caucasian populations. However, this association between rs2032582 and steroid resistance was not robust enough to withstand corrections for multiple comparisons. Similarly, we found that the rs1128503T-rs2032582G-rs1045642C (T-G-C) haplotype was associated with an increased risk of steroid resistance (OR = 2.02, 95% CI = 1.13-3.59), while the wild-type C-G-C haplotype was associated with a decreased risk (OR = 0.32, 95% CI = 0.12-0.88) in Caucasians; however, these findings were not significant following adjustments for multiple comparisons. CONCLUSIONS: MDR1 rs1128503, rs1045642, and rs2032582 polymorphisms are not associated with INS susceptibility; however, there is evidence of an association between rs1128503 and increased risk of steroid resistance in children with INS, which indicates MDR1 may play a role in steroid resistance found in children with INS.

Effects of Chinese herbal medicine Yiqi Huaju Qingli Formula in metabolic syndrome patients with microalbuminuria: a randomized placebo-controlled trial.

BACKGROUND: Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE: To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty patients with MetS were randomized into the Chinese herbal formula group (CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine) and control group (placebo in combination with Western medicine). All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES: Urinary microalbumin (MA), urinary albumin-to-creatinine ratio (UACR), 24-hour total urine protein (24-hTP), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2-hPPG), glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), blood lipid profile and blood pressure were observed. RESULTS: Compared with the control group, CHF treatment significantly decreased BMI (P<0.05), WC (P<0.01) and WHR (P<0.01). Both groups had significant decreases in FPG, 2-hPPG, HbA1c, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment (P<0.05). Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol (TAG), and a greater reduction in TAG was observed with CHF treatment (P<0.05). The level of high-density lipoprotein cholesterol did not change in the control group after treatment (P>0.05), whereas it significantly increased with CHF treatment (P<0.01). Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups (P<0.01). However, there was no significant difference between the two groups (P>0.05). CONCLUSION: Combined treatment of Yiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.

Effects of Chinese herbal medicine Yiqi Huaju Formula on hypertensive patients with metabolic syndrome: a randomized, placebo-controlled trial.

BACKGROUND: Patients with hypertension coupled with metabolic syndrome (MetS) are among the high risk population in cardiovascular and cerebrovascular diseases. To reduce the prevalence of cardiovascular and cerebrovascular diseases, it is essential to appropriately control blood pressure together with other cardiovascular risk factors. OBJECTIVE: The current study was designed to investigate the therapeutic effects on blood pressure, blood pressure variability and other cardiovascular risk factors by giving Yiqi Huaju Formula, a compound traditional Chinese herbal medicine, in addition to routine treatment to hypertensive patients coupled with MetS. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 43 patients with hypertension coupled with MetS were recruited into this study. The enrolled patients were randomly divided into the Chinese herbal formula group (anti-hypertensive drugs plus Yiqi Huaju Formula, CHF) and the control group (anti-hypertensive drugs plus placebo). The CHF group enrolled 22 patients while the control group received 21 cases. Treatments were given for 12 weeks in both groups. MAIN OUTCOME MEASURES: Parameters examined include 24-hour ambulatory blood pressure monitoring, body mass index, waist circumference, waist-to-hip ratio, homeostatic model assessment for insulin resistance (HOMA-IR), fasting glycosylated hemoglobin (HbA1c), fasting plasma glucose, 2-hour postprandial plasma glucose (PPG), fasting plasma insulin, serum lipid, etc. RESULTS: Compared with the control group, the CHF group had significant improvement (P<0.01) in anthropometric parameters, FPG, HOMA-IR, blood pressure amplitude, blood pressure variability and blood pressure load. CONCLUSION: This study showed that integrated traditional Chinese and Western medicine treatment can achieve better results in controlling blood pressure as well as other cardiovascular risk factors. The mechanism of controlling of blood pressure may be associated with the improvement of insulin sensitivity due to the Yiqi Huaju intervention. TRIAL REGISTRATION IDENTIFIER: ChiCTR-TRC-11001633.

[Clinical immunological study on prevention and treatment of chronic pyelonephritis with yishenkang granule].

OBJECTIVE: To investigate the relationship between chronic pyelonephritis (CPN) and immune function, and the therapeutic mechanism of Yishenkang granule (YSKG). METHODS: One hundred and twenty patients of CPN were divided into 3 groups randomly, the YSKG group (treated with YSKG), the control A group (treated with Sanjin tablet) and the control B group (treated with western medicine). Serum levels of immunoglobulin (Ig), complement 3 (C3), interleukin-2 (IL-2), peripheral T-lymphocyte subsets, and urinary secretory immunoglobulin A (sIgA) were determined before and after treatment with monoclonal antibody assay, agar diffusion method, radioimmunoassay (RIA), and radioimmuno-equilibrium method, and compared with normal control. RESULTS: There were disorders of T-lymphocyte subsets in CPN, lowering of serum Ig, C3 and urinary sIgA, and increase of blood IL-2 (P < 0.05 or P < 0.01). These abnormalities could be normalized after YSKG treatment. CONCLUSION: Functional disorders of cellular and humoral immunity exist in CPN patients of chronic stage, YSKG could correct the immune functional disorder, control the recurrence of CPN effectively and alleviate the immunopathological damage.