Reevaluating the splice-altering variant in TECTA as a cause of nonsyndromic hearing loss DFNA8/12 by functional analysis of RNA.

PURPOSE: The aim of this study was to determine the genetic cause of early onset autosomal dominant hearing loss segregating in five-generation kindred of Chinese descent and provide preimplantation genetic testing (PGT)for them. METHODS: Clinical examination, pedigree analysis and exome sequencing were carried out on the family. Minigene-based splicing analysis, in vivo RNA analysis and protein structure prediction by molecular modeling were conducted on the candidate variant. PGT for the causative variation and chromosome aneuploidis based on SNP analysis has been used for avoidance of hearing loss in this family. RESULTS: All the affected individuals presented with moderate down-sloping hearing loss and whole-exome sequencing identified a novel splice-site variant c.5383+6T>A in the tested subjects within the TECTA locus. Genotyping of all the 32 family members confirmed segregation of this variant and the hearing loss phenotype in the extended family. Functional analysis of RNA and molecular modeling indicates that c.5383+6T>A is a pathogenic splice-site variant and should be considered as genetic cause of the hearing loss. Furthermore, a successful singleton pregnancy with no variation in TECTA c.5383+6 was established and a healthy male child was born by PGT. CONCLUSION: We have identified a novel variant c.5383+6T>A in TECTA ZA-ZP inter-domain, which could be attributable to the early-onset autosomal dominant hearing loss. The implications of our study are valuable in elucidating the disrupted RNA splicing and uncovering the genetic cause of hearing loss with TECTA pathogenic variants, as well as providing reproductive approaches to healthy offspring.

Traditional Chinese medicine invigorating the spleen and kidney promotes HBsAg seroclearance in the mouse model.

Traditional Chinese medicine (TCM) is often used as an adjuvant or alternative therapy for abnormal liver biochemistry or liver fibrosis associated with chronic hepatitis B (CHB). However, the role of TCM in HBsAg seroclearance remains unclear. We aimed at exploring the role and possible mechanisms of TCM in HBsAg seroclearance. Fifteen widely used TCM granules invigorating the spleen and kidneys were screened. C57BL/6J mice were administered daily with TCM granules by gavage for 1 week. The effect of TCM on the M1 polarization of macrophages was measured using a CD86 assay. According to the principles of formulating prescriptions, three single TCM with the most noticeable effect on M1 polarization, accompanied by two other TCM granules, were used to develop a TCM formula. The hepatitis B virus-expressing mouse model was constructed by hydrodynamic injection of the pAAV/HBV1.2 plasmid. Hepatitis B virus-expressing mice were gavaged daily with phosphate-buffered saline (PBS), TCM formula, or Codonopsis Radix, for 1 week. HBsAg, HBeAg, and hepatitis B virus DNA levels were measured. In addition, gut microbiota was profiled using 16S rDNA sequencing. Several TCM granules showed significant effects on M1 polarization. The TCM formula accelerated HBsAg seroclearance compared with the Codonopsis Radix and PBS groups. Intrahepatic M1 polarization, as indicated by flow cytometry and immunohistochemistry, was induced in the TCM formula and Codonopsis Radix groups. The abundance of Alloprevotella significantly increased in the TCM formula and Codonopsis Radix groups. These results demonstrate that the TCM formula for invigorating the spleen and kidney can accelerate HBsAg seroclearance. This effect can be attributed, at least in part, to M1 polarization of intrahepatic macrophages.

Two ambuic acid dimers derived from homo-endo Diels-Alder reaction from Pestalotiopsis versicolor.

Two new dimers of ambuic acid, pestaloversicoloric acids A (1) and B (2), and a known derivative, 13(S)-hydroxyambuic acid (3), were isolated from the static fermentation product of Pestalotiopsis versicolor. The structural identification was accomplished via analyses on the data of HR-MS, 1 D and 2 D NMR, and ECD. Different from the well-known exo-type dimer, torreyanic acid, compounds 1 and 2 represent the first example of endo-type product derived from the intermolecular Diels-Alder reaction of two molecules of ambuic acid derivative with the identical absolute stereochemistry.

Increased circulating sclerostin levels in rheumatoid arthritis patients: an updated meta-analysis.

BACKGROUND: Sclerostin, a regulator of bone metabolism and vascular calcification involved in regulating the Wnt/ß-catenin signaling pathway, has been shown to be involved in the pathogenesis of rheumatoid arthritis (RA). However, current results regarding the circulating sclerostin level of RA patients are debatable. This study aimed to evaluate the circulating level of sclerostin in RA patients and briefly summarize its role. METHOD: PubMed, EMBASE, and the Cochrane Library databases were systematically searched till May 27, 2021, for eligible articles. Useful data from all qualified papers were systematically extracted and analyzed using Stata 12.0 software (Stata Corp LP, College Station, TX, USA). RESULTS: Overall, 13 qualifying studies including 1030 cases and 561 normal controls were analyzed in this updated meta-analysis. Forest plot of this meta-analysis showed that RA patients had higher circulating sclerostin levels (P < 0.001, standardized mean difference [SMD] = 0.916, 95% CI: 0.235-1.597) compared to normal controls. Subgroup analyses implied that age, region, and assay method were associated with sclerostin level in RA patients. CONCLUSION: RA patients have higher circulating sclerostin levels, and these was influenced by age, region, and assay method.

Beyond C3N4 π-conjugated metal-free polymeric semiconductors for photocatalytic chemical transformations.

Photocatalysis with stable, efficient and inexpensive metal-free catalysts is one of the most promising options for non-polluting energy production. This review article covers the state-of-the-art development of various effective metal-free polymeric photocatalysts with large π-conjugated units for chemical transformations including water splitting, CO2 and N2 reduction, organic synthesis and monomer polymerisation. The article starts with the catalytic mechanisms of metal-free photocatalysts. Then a particular focus is on the rational manipulation of π-conjugation enlargement, charge separation, electronic structures and band structures in the design of metal-free polymeric photocatalysts. Following the design principles, the selection and construction of functional units are discussed, as well as the connecting bonds and dimensions of π-conjugated polymeric photocatalysts. Finally the hot and emerging applications of metal-free polymeric photocatalysts for photocatalytic chemical transformations are summarized. The strategies provide potential avenues to address the challenges of catalyst activity, selectivity and stability in the further development of highly effective metal-free polymeric photocatalysts.

Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990-2019.

BACKGROUND & AIMS: Acute viral hepatitis (AVH) represents an important global health problem; however, the progress in understanding AVH is limited because of the priority of combating persistent HBV and HCV infections. Therefore, an improved understanding of the burden of AVH is required to help design strategies for global intervention. METHODS: Data on 4 major AVH types, including acute hepatitis A, B, C, and E, excluding D, were collected by the Global Burden of Disease (GBD) 2019 database. Age-standardized incidence rates and disability-adjusted life year (DALY) rates for AVH were extracted from GBD 2019 and stratified by sex, level of socio-demographic index (SDI), country, and territory. The association between the burden of AVH and socioeconomic development status, as represented by the SDI, was described. RESULTS: In 2019, there was an age-standardized incidence rate of 3,615.9 (95% CI 3,360.5-3,888.3) and an age-standardized DALY rate of 58.0 (47.3-70.0) per 100,000 person-years for the 4 major types of AVH. Among the major AVH types, acute hepatitis A caused the heaviest burden. There was a significant downward trend in age-standardized DALY rates caused by major incidences of AVH between 1990 and 2019. In 2019, regions or countries located in West and East Africa exhibited the highest age-standardized incidence rates of the 4 major AVH types. These rates were stratified by SDI: high SDI and high-middle SDI locations recorded the lowest incidence and DALY rates of AVH, whereas the low-middle SDI and low SDI locations showed the highest burden of AVH. CONCLUSIONS: The socioeconomic development status and burden of AVH are associated. Therefore, the GBD 2019 data should be used by policymakers to guide cost-effective interventions for AVH. LAY SUMMARY: We identified a negative association between socioeconomic development status and the burden of acute viral hepatitis. The lowest burden of acute viral hepatitis was noted for rich countries, whereas the highest burden of acute viral hepatitis was noted for poor countries.

Circulating adiponectin levels and systemic lupus erythematosus: a two-sample Mendelian randomization study.

OBJECTIVES: Several studies have reported increased serum/plasma adiponectin levels in SLE patients. This study was performed to estimate the causal effects of circulating adiponectin levels on SLE. METHODS: We selected nine independent single-nucleotide polymorphisms that were associated with circulating adiponectin levels (P < 5 × 10-8) as instrumental variables from a published genome-wide association study (GWAS) meta-analysis. The corresponding effects between instrumental variables and outcome (SLE) were obtained from an SLE GWAS analysis, including 7219 cases with 15 991 controls of European ancestry. Two-sample Mendelian randomization (MR) analyses with inverse-variance weighted, MR-Egger regression, weighted median and weight mode methods were used to evaluate the causal effects. RESULTS: The results of inverse-variance weighted methods showed no significantly causal associations of genetically predicted circulating adiponectin levels and the risk for SLE, with an odds ratio (OR) of 1.38 (95% CI 0.91, 1.35; P = 0.130). MR-Egger [OR 1.62 (95% CI 0.85, 1.54), P = 0.195], weighted median [OR 1.37 (95% CI 0.82, 1.35), P = 0.235) and weighted mode methods [OR 1.39 (95% CI 0.86, 1.38), P = 0.219] also supported no significant associations of circulating adiponectin levels and the risk for SLE. Furthermore, MR analyses in using SLE-associated single-nucleotide polymorphisms as an instrumental variable showed no associations of genetically predicted risk of SLE with circulating adiponectin levels. CONCLUSION: Our study did not find evidence for a causal relationship between circulating adiponectin levels and the risk of SLE or of a causal effect of SLE on circulating adiponectin levels.

LncRNA NEAT1 accelerates renal tubular epithelial cell damage by modulating mitophagy via miR-150-5p-DRP1 axis in diabetic nephropathy.

NEW FINDINGS: What is the central question of this study? Diabetic nephropathy (DN) is a severe complication of diabetes correlated with a higher mortality rate in diabetic patients. Renal tubular injury participates in the pathogenesis of DN. We aimed to uncover the biological function of the NEAT1-miR-150-5p-DRP1 axis in an in vitro model of DN and elaborate the potential mechanisms. What is the main finding and its importance? NEAT1 facilitated high glucose-induced damage in HK-2 cells by reducing mitophagy via the miR-150-5p-DRP1 axis, which sheds light on DN pathogenesis and reveals a potential treatment for DN. ABSTRACT: Diabetic nephropathy (DN) is a severe complication in diabetic patients, with a high mortality rate. Renal tubular injury is involved in the pathogenesis of DN. In this study, we aimed to uncover the regulatory roles of the NEAT1-miR-150-5p-DRP1 axis in an in vitro model of DN and its possible mechanisms. High glucose-challenged HK-2 cells were used as an in vitro DN model. NEAT1, miR-150-5p and DRP1 levels were assessed by RT-qPCR. Cell viability was determined by the MTT assay. MitoSOX Red and JC-1 were used to evaluate intracellular production of reactive oxygen species and mitochondrial membrane potential, respectively. Lactate dehydrogenase release and superoxide dismutase activity were assessed with commercial kits. The protein levels of DRP1, p62, BECN1(beclin 1) and BNIP3 were determined by western blotting. The interaction between NEAT1 (DRP1) and miR-150-5p was verified by a dual-luciferase reporter assay and an RNA immunoprecipitation assay. Our results showed that in response to high glucose the NEAT1 and DRP1 levels were upregulated, whereas the miR-150-5p level was downregulated in HK-2 cells. Knockdown of NEAT1 or DRP1 in high glucose-challenged HK-2 cells inhibited excessive reactive oxygen species production and lactate dehydrogenase release, increased cell viability, mitochondrial membrane potential and superoxide dismutase activity and enhanced mitophagy. Inhibition of miR-150-5p resulted in the opposite results. Mechanistically, NEAT1 sponged miR-150-5p to increase the DRP1 level. Moreover, silencing of NEAT1 or DRP1 could counteract miR-150-5p inhibition-induced deleterious effects. Collectively, our findings indicate that NEAT1 facilitates high glucose-induced damage in HK-2 cells by suppressing mitophagy via the miR-150-5p-DRP 1 axis, which sheds light on a novel mechanism of DN.

Association of PER2 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

The circadian clock plays a crucial role in the progress of systemic lupus erythematosus (SLE). In this study, we performed a case-control study to explore the association between Period 2 (PER2) gene single nucleotide polymorphisms (SNPs) and the susceptibility of systemic lupus erythematosus (SLE). A total of 492 SLE patients and 493 healthy controls were included. The improved multiple ligase detection reaction (iMLDR) was used for genotyping. The correlations between four SNPs of PER2 (rs10929273, rs11894491, rs36124720, rs934945) and the genetic susceptibility and clinical manifestations of SLE were analyzed. Significant differences were observed in the distributions of allele frequencies and genotype under dominant model in rs11894491 between SLE patients and controls (p = 0.030, p = 022, respectively). We hypothesized that PER2 gene SNPs was related to the genetic susceptibility and clinical manifestations, implying the potential role of PER2 in the pathogenesis of SLE.

Seasonality and global public interest in psoriasis: an infodemiology study.

OBJECTIVE: Although patients with psoriasis frequently report seasonal changes in their symptoms, the seasonality of psoriasis has rarely been explored. This study aims to investigate the seasonal pattern of and global public interest in psoriasis using Google search data. METHODS: Internet search data were collected from Google Trends. Data on the relative search volume (RSV) from January 2004 to December 2018 were retrieved using the term psoriasis. Cosinor analyses were conducted to examine the seasonality of psoriasis using data from two southern hemisphere countries (Australia and New Zealand) and four northern hemisphere countries (USA, Canada, UK and Ireland). RESULTS: Overall, searches for psoriasis steadily decreased between 2004 and 2010, and then rose from 2011 to 2018. On cosinor analyses, RSV of 'psoriasis' displayed a significant seasonal variation worldwide (p<0.025). Further analyses confirmed the seasonality of psoriasis-related RSV in Australia, New Zealand, USA, Canada, UK and Ireland (p<0.025 for all), with peaks in the late winter/early spring months and troughs in the late summer/early autumn months. The top 11 rising topics were calcipotriol/betamethasone dipropionate, ustekinumab, apremilast, shampoo, eczema, guttate psoriasis, seborrhoeic dermatitis, dermatitis, psoriatic arthritis, atopic dermatitis and arthritis. CONCLUSION: There was a significant seasonal pattern for psoriasis, with peaks in the late winter/early spring and troughs in the late summer/early autumn. Further studies are warranted to confirm the seasonal pattern of psoriasis using clinical data and to explore the underlying mechanisms.

Impact of the updated 2018 ASCO/CAP guidelines on HER2 FISH testing in invasive breast cancer: a retrospective study of HER2 fish results of 2233 cases.

OBJECTIVES: Human epidermal growth factor receptor 2 (HER2, ERBB2) is a valuable prognostic and predictive biomarker in breast cancer. Accurate assessment of HER2 status is essential in selecting the patients with invasive breast cancer who will likely response to HER2-targeted therapies. Some major modifications in the diagnostic recommendation for fluorescence in situ hybridization (FISH) have been made in the updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline. According to the revised guideline, concomitant IHC assays are required to arrive at the most accurate HER2 status designation after HER2 FISH equivocal results; however, little is known about its influence on the clinical practice of pathologist. The purpose of this study was to evaluate the impact of the revised 2018 ASCO/CAP guidelines on the HER2 status designation. METHODS: We retrospectively reviewed the HER2 FISH testing results from 2233 cases of invasive breast cancer between January 2014 and December 2017. Concomitant immunohistochemistry (IHC) were performed on the same tissue blocks that were used for the FISH testing. RESULTS: Compared to the 2013 guidelines, the HER2 status in 183 (8.2%) cases were re-defined when reassessed by the 2018 guidelines. Among these 183 cases, 175 equivocal cases according to the 2013 guideline were re-defined as HER2 negative (n = 173) or HER2 positive (n = 2). Eight previously classified as HER2 positive cases were converted to negative in the 2018 scheme, all of which were with HER2 IHC scores of 1+ or 2+. The number of cases in the negative category was 1705 according to the 2018 guidelines as opposed to 1524 by the 2013 guidelines. CONCLUSIONS: The updated 2018 ASCO/CAP guidelines eliminated the FISH equivocal category, which can be attributed to reflex HER2 IHC, and partly ease the dilemma for clinical practice. Reflex IHC for FISH equivocal cases is of prime importance; furthermore, HER2 FISH results were converted from positivity to negativity based on the concomitant IHC results in a small percentage of cases. In all, implementation of the 2018 ASCO/CAP guidelines provides much clearer instructions and recommendations for the HER2 status designation, and thus reduces the risk of misdiagnosis.

Elevated circulating asymmetric dimethylarginine levels in rheumatoid arthritis: a systematic review and meta-analysis.

Rheumatoid arthritis (RA) patients have increased risk of cardiovascular disease (CVD) death. Elevated asymmetric dimethylarginine (ADMA) levels have been reported to be an independent predictor of CVD morbidity and mortality, however, the role of ADMA in RA remains undetermined. To derive a more accurate estimation on circulating ADMA levels in RA patients, a meta-analysis was performed. Embase, PubMed, and The Cochrane Library database (up to October 7 2018) were used to acquire published literatures. Heterogeneity test was performed by the Q statistic and quantified using I2. Publication bias was evaluated using a funnel plot and Egger's linear regression test. A total of 174 articles were identified, 16 studies with 1365 subjects (666 RA patients and 699 healthy individuals) were ultimately included. Plasma/serum ADMA levels appeared to be higher in RA patients than healthy controls (SMD = 0.84, 95% CI 0.32, 1.35). By assessing the BMI, age, disease duration and disease activity as subgroups, BMI ≥ 24 and BMI < 24 groups both showed elevated ADMA levels than controls, disease duration ≥ 8, age < 50 and disease activity ≥ 3.2 and < 5.1 group had a higher ADMA level than control groups. However, disease duration < 8, disease activity ≥ 5.1 and age ≥ 50 groups showed no difference between two groups. Circulating ADMA levels are higher in RA patients compared with healthy controls. In addition, ADMA levels are influenced by age, disease duration and disease activity.

Leveraging Google Trends to investigate the global public interest in rheumatoid arthritis.

This study aims to investigate the global public interest in rheumatoid arthritis by evaluating search term popularity changes of the disease over a decade. Google Trends was applied to retrieve search popularity scores for the term 'rheumatoid arthritis' between January 2004 and December 2017, utilizing the category of "health". Overall, relative searches volume for rheumatoid arthritis steadily decreased from January 2004 to December 2010, and then slowly rose from January 2011 to December 2017. There were significant seasonal variations in relative searches volume for the term 'rheumatoid arthritis' (Amplitude = 3.11; Phase: Month = 4.3; Low point: Month = 10.3; p < 0.025). Relative searches volume peaked in April and reached the lowest level in October. The top 11 rising topics were scleroderma, Anna Marchesini, C-reaction protein, osteoarthritis, arthritis, joint pain, autoimmune disease, rheumatoid factor, rheumatology, methotrexate, and systemic lupus erythematosus, ranking from high to low by relative growth of topic regarding rheumatoid arthritis. In conclusion, the evidence from Google Trends analysis demonstrates a significant seasonal variation in rheumatoid arthritis, with a peak in April. In addition, the top rising search queries are beneficial for physicians to search the Internet themselves for websites that provide high-quality information to recommend to their patients.

Three new polyketides from Ascotricha sp. ZJ-M-5 by the OSMAC strategy.

Three new compounds, ascotrichols A-B (1-2) and ascotrichrone A (3), along with two known isocoumarin derivatives (4-5), were isolated from the solid culture of a sea mud-derived fungus, Ascotricha sp. ZJ-M-5 on rice media. The structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR data, and the absolute configurations were determined by electronic circular dichroism and biogenetic correlation.

Polyketides from Pestalotiopsis zonata and structure revision of pestalrones A and B.

The structures of pestalrones A-B were revised via reinterpretation of the NMR data and a brief chemical transformation from the co-occurring polyketides, in our investigation on the secondary metabolites of Pestalotiopsis zonata, which also afforded a new α-pyrone derivative, pestazonatic acid, and four known analogs.

[The Roles of Icariin on the Proliferation and Apoptosis Abilities of Human Oophoroma Cells and Multi-drug Resistant Cell Line].

OBJECTIVE: To explore the effects of icariin on the proliferation and apoptosis abilities of human ovarian cancer cells SKOV3 and multi-drug resistant SKVCR cells. METHODS: Human ovarian cancer cells SKOV3 and multi-drug resistant SKVCR cells were treated with various concentrations of icariin. The inhibitory concentration and the half maximal inhibitory concentration were detected by CCK8 kit. The proliferation and apoptosis abilities of SKOV3 and SKVCR cells were measured by flow cytometry. The migration and invasion abilities of SKOV3 and SKVCR cells were evaluated by Transwell assays. The protein expression level of Caspase-3 was detected by Western blot analysis. RESULTS: Icariin significantly suppressed the proliferation abilities of SKOV3 and SKVCR cells in a dose-dependent manner at variant levels from 5-100 µg/mL. SKOV3 and SKVCR cells were treated with 19.5 µg/mL icariin and 48.4 µg/mL icariin (0.8×IC50) for 48 h, respectively. The results showed that the cell proliferation, migration and invasion abilities were markedly decreased comparing with control group, and the apoptosis rate was significantly increased as compared with control group (P<0.05). Western blot results indicated that icariin significantly increased the protein expression level of caspase-3 in SKOV3 and SKVCR cells (P<0.05). CONCLUSION: Icariin suppressed the proliferation, migration and invasion abilities of human ovarian cancer cells. Increasing expression of Caspase-3 might be the mechanism of its enhancement of apoptosis.

Impact of repeat HER2 testing after initial equivocal HER2 FISH results using 2013 ASCO/CAP guidelines.

PURPOSE: The updated 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing have made some major changes in HER2 fluorescence in situ hybridization (FISH) interpretation criteria with additional FISH equivocal cases. Repeat HER2 testing is recommended after initial HER2 FISH equivocal results; however, little is known about its impact on final HER2 status. The aim of this study is to investigate whether reflex test clarifies HER2 status, and to characterize clinicopathological features of the newly defined HER2 equivocal group. METHODS: A total of 886 consecutive cases of primary invasive breast cancer conducted with dual-probe HER2 FISH testing between November 2013 and December 2015 were reviewed. HER2 immunohistochemistry (IHC) and FISH testing were performed on a different tissue block or a new specimen after initial HER2 FISH equivocal results. RESULTS: Compared to 2007 guideline, 85 (9.6%) cases changed their category by using 2013 guideline. The major change of the 85 cases is that 57 (6.4%) cases in HER2 FISH-negative category changed to equivocal, and the equivocal category cases increased from 36 to 67. HER2 FISH equivocal was significantly associated with HER2 IHC equivocal (2+) and chromosome 17 polysomy (P < 0.01). Repeat testing by IHC and FISH clarified HER2 status in 33 and 42% of HER2 equivocal cases, respectively. Overall 32 (48%) initial HER2 equivocal cases stayed HER2 equivocal after repeat FISH and or IHC testing. These tumors were ER/PR+, with high KI-67 index. CONCLUSION: New guidelines classify more HER2 FISH equivocal cases. Repeat HER2 testing clarifies HER2 status in about 50% of initial HER2 FISH equivocal cases. In addition, HER2 equivocal cases merit further study as there is limited information about prognosis and optimal treatment strategy for this population.

Two new threitol orsellinates from a sea mud-derived fungus, Ascotricha sp. ZJ-M-5.

Two new d-threitol orsellinates (1-2) were isolated from the EtOAc extract of a sea mud-derived fungus, Ascotricha sp. ZJ-M-5, cultured in Czapek Dox broth. These two compounds featured in the symmetrical substitution of orsellinic acid or acetic acid, which was established on the basis of 1D and 2D NMR experiments. The characteristic optical rotations enabled the assignment of the absolute configuration.

[Pharmacokinetics of mercury after oral administration of cinnabaris and Fufang Niuhuang Xiaoyan capsule in rats].

Fufang Niuhuang Xiaoyan capsule was a classical compound prescription with the efficacy of heat-clearing, detoxification, sedation and anti-inflammation, with cinnabaris as one of its active ingredients. The study focuses on the pharmacokinetics of mercury in rats after oral administration of cinnabaris and Fufang Niuhuang Xiaoyan capsule, in order to explore the effect of combined traditional Chinese medicines on mercury metabolism. In this study, the method of nitric-perchloric acid digestion system coupled with cold atomic-atomic fluorescence spectroscopy (CV-AFS) was adopted to accurately determine mercury in whole blood of rats. Fufang Niuhueng Xiaoyan capsule had three dose schemes of oral administration, namely equivalent clinical dose, 3 times of equivalent clinical dose and 10 times of equivalent clinical dose; And the doses of oral administration of cinnabaris was calculated according to that of Fufang Niuhuang Xiaoyan capsule. SPF grade healthy SD rats were fasted overnight before the oral administration with cinnabaris suspension (or Fufang Niuhuang Xiaoyan capsule suspension). After oral administration of different doses of cinnabaris, no obvious changes in tmax and MRT were observed, while Cmax/dose, AUC0-48 h/dose and AUC0-∞/dose decreased with the increase in dose, indicating that total mercury absorption in body was declining. As the dose increased, Ke, CL/F decreased, and t1/2 increased, indicating that the elimination slowed down, and mercury metabolism showed non-linear dynamic characteristics within a certain range of dose (22-220 mg•kg⁻¹). The total mercury metabolism in the whole blood of rats after oral administration with different doses of Fufang Niuhuang Xiaoyan capsule also showed non-linear dynamic characteristics. The results were correlated with the low solubility of cinnabaris in the body. Compared with cinnabaris, Fufang Niuhuang Xiaoyan capsule showed no obvious changes in V/F and MRT, while Ke, CL/F, tmax decreased, and t1/2, Cmax/dose, AUC0-48 h/dose, AUC0-∞/dose increased significantly. The results showed that Fufang Niuhuang Xiaoyan capsule accelerated absorption, slowed down elimination and improved the total absorption of mercury in the whole blood, indicating that Fufang Niuhuang Xiaoyan capsule may contain components for promoting absorption and alleviating elimination of mercury. Fufang Niuhuang Xiaoyan capsule had an impact on the pharmacokinetics of cinnabaris, and long-term administration of cinnabaris (Fufang Niuhuang Xiaoyan capsule) was possible to cause accumulation of mercury in the body. This study could explain changes in efficacy of Fufang Niuhuang Xiaoyan capsule, evaluate the rationality of compound medicines containing toxic elements and provide scientific basis for the rational and safe use of Fufang Niuhuang Xiaoyan capsule.

[Neoflavonoids and their pharmacological activities in Dalbergia genus].

Neoflavonoids are a kind of characteristic components in the Dalbergia genus. Based on the previous researches, 59 neoflavonoids have been obtained from the Dalbergia genus. According to their molecular skeleton, the neoflavonoids can be divided intodalbergiphenols, dalbergiones, dalbergins, benzophenones and other types. Modern research shows that neoflavonoids displayed a variety of pharmacological activities, such as anti-osteoporosis, anti-inflammatory, antitumor, anti-androgen, anti-allergic, antioxidation etc. This paper reviewed neoflavonoids and their pharmacological functions, which could provide the valuable reference for comprehensive utilization and new drug development in the Dalbergia genus.