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Liu Wei Di Huang Wan (LDW), a well-known traditional Chinese medicine, is widely used for the treatment of various diseases in China. This study was designed to investigate the potential herb–drug interactions of LDW in healthy volunteers and attempted to ascertain whether the interaction might be affected by genotypes. We assessed the effect of LDW on the activities of CYP2C19, CYP2D6 and CYP3A4 in 12 Chinese healthy subjects in a single-center, controlled, non-blinded, two-way crossover clinical trial. The subject pool consisted of six extensive metabolizers with CYP2C19*1/*1 and six poor metabolizers with CYP2C19*2/*2. Placebo or 4.8 g LDW (12 pills, 0.2 g/pill, twice daily) was given to each participant for 14 continuous days with a wash-out period of 2 weeks after an oral administration of 30 mg omeprazole, 30 mg dextromethorphan hydrobromide and 7.5 mg midazolam. The activities of CYP2C19, CYP2D6 and CYP3A4 were ascertained by their respective plasma or urinary metabolic ratios on day 14 post-treatment. There is no difference in the activities of the three tested enzymes before or after a 14-day administration of LDW. LDW had no effect on the pharmacokinetic parameters of the substrates and their metabolites. A 14-day administration of LDW did not affect the activities of CYP2C19, CYP2D6 and CYP3A4. LDW is unlikely to cause pharmacokinetic interaction when it is combined with other medications predominantly metabolized by these enzymes. [ABSTRACT FROM AUTHOR]

Plum ( Prunus salicina Lindl.) is commercially cultivated worldwide for the high levels of nutrients in the fruit. In recent years, anthracnose has been severe in some plum planting areas in China, resulting in a large number of necrotic leaves, blight, and premature leaf fall. In this study, anthracnose samples of plum leaves were collected from Hezhou, Guilin, and Lipu in Guangxi Province and Meishan, Abe Tibetan, and Qiang Autonomous Prefecture of Sichuan Province. Characteristics of mycelia on potato dextrose agar, morphology of appressoria and conidia, and analysis of sequences of several marker regions (internal transcribed spacer [ITS] region, glyceraldehyde-3-phosphate dehydrogenase [ GAPDH ], chitin synthase [ CHS-1 ], histone H3 [ HIS3 ], actin [ ACT ], β-tubulin [ TUB2 ], and the intergenic region between apn2 and MAT1-2-1 [ApMat]). The resulting 101 Colletotrichum isolates obtained were identified as eight species: C. fructicola (50.5%), C. siamense (24.8%), C. karsti (8.9%), C. plurivorum (7.9%), C. aeschynomenes (3.9%), C. gloeosporioides (2%), C. celtidis (1%), and C. phyllanthi (1%). Representatives of all eight Colletotrichum species were found to cause disease on wounded leaves of plum seedlings in pathogenicity assays. As far as we are aware, this is the first report of anthracnose of plum caused by C. celtidis and C. phyllanthi in China., Competing Interests: The author(s) declare no conflict of interest.

In order to comprehensively evaluate the environmental impact of multi-media mercury pollution under differentiated emission control strategies in China, a literature review and case studies were carried out. Increased human exposure to methylmercury was assessed through the dietary intake of residents in areas surrounding a typical coal-fired power plant and a zinc (Zn) smelter, located either on acid soil with paddy growth in southern China, or on alkaline soil with wheat growth in northern China. Combined with knowledge on speciated mercury in flue gas and the fate of mercury in the wastewater or solid waste of the typical emitters applying different air pollution control devices, a simplified model was developed by estimating the incremental daily intake of methylmercury from both local and global pollution. Results indicated that air pollution control for coal-fired power plants and Zn smelters can greatly reduce health risks from mercury pollution, mainly through a reduction in global methylmercury exposure, but could unfortunately induce local methylmercury exposure by transferring more mercury from flue gas to wastewater or solid waste, then contaminating surrounding soil, and thus increasing dietary intake via crops. Therefore, tightening air emission control is conducive to reducing the comprehensive health risk, while the environmental equity between local and global pollution control should be fully considered. Rice in the south tends to have higher bioconcentration factors than wheat in the north, implying the great importance of strengthening local pollution control in the south, especially for Zn smelters with higher contribution to local pollution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2022. Published by Elsevier B.V.)

Aim: This article aims to quantitatively analyze the growth trend of listed pharmaceutical companies in the US and China by a machine learning algorithm., Background: In the last two decades, the global pharmaceutical industry has faced the dilemma of low research & development (R&D) success rate. The US is the world's largest pharmaceutical market, while China is the largest emerging market., Objective: To collect data from the database and apply machine learning to build the model., Methods: LightGBM algorithm was used to build the model and identify the factor important to the performance of pharmaceutical companies., Results: The prediction accuracy for US companies was 80.3%, while it was 64.9% for Chinese companies. The feature importance shows that the net profit growth rate and debt liability ratio are significant in financial indicators. The results indicated that the US may continue to dominate the global pharmaceutical industry, while several Chinese pharmaceutical companies rose sharply after 2015 with the narrowing gap between the Chinese and US pharmaceutical industries., Conclusion: In summary, our research quantitatively analyzed the growth trend of listed pharmaceutical companies in the US and China by a machine learning algorithm, which provide a novel perspective for the global pharmaceutical industry. According to the R&D capability and profitability, 141 US-listed and 129 China-listed pharmaceutical companies were divided into four levels to evaluate the growth trend of pharmaceutical firms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Doxepin, a tricyclic antidepressant (TCA), is widely used in the treatment of depressive disorder and anxiety. There are some liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods that have been reported for detecting doxepin, but inadequacies in recovery and cumbersome sample preparation obstruct the pharmacokinetics study. Therefore, we aimed to develop and validate a rapid sample preparation method based on solid-phase extraction (SPE) for the precise quantification of doxepin and its metabolites. Chromatography separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) and a mobile phase consisting of 70% of mobile phase A (0.1% formic acid and 10 mM ammonium formate) and 30% mobile phase B (0.1% formic acid in acetonitrile) at a flow rate of 0.4 mL min -1 in the step gradient elution conditions. The lower limits of quantification for doxepin and N -nordoxepin were 4 pg mL -1 and 2 pg mL -1 , respectively. This method was validated with satisfactory results including good precision and accuracy. A rapid, sensitive, and specific LC-MS/MS method was developed and validated for the determination of doxepin in human plasma. This method could be applied for determining doxepin and N -nordoxepin concentrations in plasma that could be useful for bioequivalence study of 3 mg doxepin.

Mercury pollution has attracted worldwide attention due to its toxicity, bioaccumulation and persistence. Cement clinker production is the top emitter of atmospheric mercury in China and the emissions from raw mill systems account for about 85% of all emissions. However, the mercury emission characteristics and mechanisms as a function of time during an operation cycle are still unclear. This study aims to reveal the mercury emission characteristics and mechanisms in cement plants by comprehensively using offline and online field measurements, control experiments and heat transfer analysis. Research results indicated that an intermediate temperature (300-500 °C) desorption and the heterogeneous oxidation of mercury in the precalciner, the selective adsorption of oxidized gaseous mercury (Hg 2+ ) to raw meal, and Hg 2+ re-vaporization in the conditioning tower jointly caused an increase in the Hg 2+ ratio (15.3%-83.6%) during the mill-off mode. In addition, mercury concentrations remained at approximately 6.5 μg/Nm 3 during the mill-on mode while the values reached a peak of 1835.4 μg/Nm 3 during the mill-off mode. Thus, atmospheric mercury emissions during the mill-off mode accounted for 35.0%- 71.7% of the emissions during the entire cycle, although the mill-off period only lasted for 5%- 17% of the whole cycle. Our results therefore suggest that supervisory monitoring of mercury in cement clinker production should specify the operating status of raw mills. Mercury control technologies targeting a relatively short period for the mill-off mode can substantially reduce mercury emissions from cement clinker production, and thus, the related impacts on ecosystems and human health., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Coal preparation is effective in controlling primary mercury emissions in coal combustion systems; however, the combustion of coal preparation byproducts may cause secondary emissions. The inconsistent coal preparation statistics, unclear mercury distribution characteristics during coal preparation, and limited information regarding the byproduct utilization pathways lead to great uncertainty in the evaluation of the effect of coal preparation in China. This study elucidated the mercury distribution in coal preparation based on the activity levels of 2886 coal preparation plants, coal mercury content database, tested mercury distribution factors of typical plants, and then traced the mercury flows and emissions in the downstream sectors using a cross-industry mercury flow model. We found that coal preparation altered the mercury flows by reducing 68 tonnes of mercury to sectors such as coking and increasing the flows to byproduct utilization sectors. Combusting cleaned coal rather than raw coal reduced the mercury emissions by 47 tonnes; however, this was offset by secondary mercury emissions. Coal gangue spontaneous combustion and the cement kiln coprocessing process were dominant secondary emitters. Our results highlight the necessity of whole-process emission control of atmospheric mercury based on flow maps. Future comprehensive utilization of wastes in China should fully evaluate the potential secondary mercury emissions.

This study developed an up-to-date and point-source-based inventory of mercury (Hg) releases to water in China by applying probabilistic release factors that combined industry removal efficiencies, reuse of reclaimed water, and receiving water types. In 2017, the national mercury release to water was estimated to be 50 (35-66) tons, in which 47%, 8%, 7%, and 25% were from nonferrous metal smelting, vinyl chloride monomer (VCM) production, coal-fired boilers, and domestic sewage, respectively. Approximately 95% of mercury was released to inland rivers, and the rest was discharged to lakes or coastal water. The significant sources were identified based on their mercury releases to water. The control of mercury release to water in China shall focus on zinc smelting plants, municipal sewage treatment plants, and the VCM production process. For zinc smelting plants, China can tighten the limit of mercury concentration in discharged wastewater and combine Hg-catcher device in traditional integrated treatment. For municipal sewage treatment plants and the VCM production process, promoting processes of Hg-free production can reduce mercury inputs at the source. Our study provides insights for other parties to identify the relevant sources of mercury release to water and to conduct control measures, so as to promote the global convention implementation.

The promise of speech disorders as biomarkers in clinical examination has been identified in a broad spectrum of neurodegenerative diseases. However, to the best of our knowledge, a validated acoustic marker with established discriminative and evaluative properties has not yet been developed for oral tongue cancers. Here we cross-sectionally collected a screening dataset that included acoustic parameters extracted from 3 sustained vowels /ɑ/, /i/, /u/ and binary perceptual outcomes from 12 consonant-vowel syllables. We used a support vector machine with linear kernel function within this dataset to identify the formant centralization ratio (FCR) as a dominant predictor of different perceptual outcomes across gender and syllable. The Acoustic analysis, Perceptual evaluation and Quality of Life assessment (APeQoL) was used to validate the FCR in 33 patients with primary resectable oral tongue cancers. Measurements were taken before (pre-op) and four to six weeks after (post-op) surgery. The speech handicap index (SHI), a speech-specific questionnaire, was also administrated at these time points. Pre-op correlation analysis within the APeQoL revealed overall consistency and a strong correlation between FCR and SHI scores. FCRs also increased significantly with increasing T classification pre-operatively, especially for women. Longitudinally, the main effects of T classification, the extent of resection, and their interaction effects with time (pre-op vs. post-op) on FCRs were all significant. For pre-operative FCR, after merging the two datasets, a cut-off value of 0.970 produced an AUC of 0.861 (95% confidence interval: 0.785-0.938) for T 3-4 patients. In sum, this study determined that FCR is an acoustic marker with the potential to detect disease and related speech function in oral tongue cancers. These are preliminary findings that need to be replicated in longitudinal studies and/or larger cohorts., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Controlling anthropogenic mercury emissions is an ongoing effort and the effect of atmospheric mercury mitigation is expected to be impacted by accelerating climate change. The lockdown measures to restrict the spread of Coronavirus Disease 2019 (COVID-19) and the following unfavorable meteorology in Beijing provided a natural experiment to examine how air mercury responds to strict control measures when the climate becomes humid and warm. Based on a high-time resolution emission inventory and generalized additive model, we found that air mercury concentration responded almost linearly to the changes in mercury emissions when excluding the impact of other factors. Existing pollution control and additional lockdown measures reduced mercury emissions by 16.7 and 12.5 kg/d during lockdown, respectively, which correspondingly reduced the concentrations of atmospheric mercury by 0.10 and 0.07 ng/m 3 . Emission reductions from cement clinker production contributed to the largest decrease in atmospheric mercury, implying potential mitigation effects in this sector since it is currently the number one emitter in China. However, changes in meteorology raised atmospheric mercury by 0.41 ng/m 3 . The increases in relative humidity (9.5%) and temperature (1.2 °C) significantly offset the effect of emission reduction by 0.17 and 0.09 ng/m 3 , respectively, which highlights the challenge of air mercury control in humid and warm weather and the significance of understanding mercury behavior in the atmosphere and at atmospheric interfaces, especially the impact from relative humidity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Choline is an important nutrient involved in multiple biosynthesis pathways. However, whether circulating choline levels are associated with the risk of hypertension (HTN) and artery stenosis in HTN remains unknown. We investigated the correlations of plasma choline with HTN and coronary artery injury and explored the utility of plasma choline as a diagnostic biomarker for HTN and artery stenosis. 193 HTN patients and 154 age- and sex-matched healthy controls (CON) were recruited in this study. Fasting plasma choline was detected using liquid chromatography tandem mass spectrometry. Choline levels were significantly higher in HTN without artery stenosis (HTN-AS) than CON (8.07 [7.19-9.24] μM vs 7.03 [6.21-8.13] μM, P < .01) group and were further upregulated in HTN with artery stenosis (HTN + AS) (8.63 [7.09-10.59] μM, P < .01) group. Patients with multivessel disease (MVD) also exhibited higher choline levels than those with single vessel disease (SVD) (8.64 [7.16-10.55] μM vs 8.04(6.74-9.38) μM, P < .01). Increased choline levels were independently associated with the risk of HTN (OR = 1.2, 95% CI: 1-1.45, P = .05), HTN + AS (OR = 1.27, 95% CI: 1.09-1.48, P < .01), and MVD (OR = 1.16, 95% CI: 1.02-1.31, P = .02) after adjustment for multiple risk factors. Receiver operating characteristic (ROC) analysis showed that choline had an area under curve (AUC) score of 0.69, 0.67, and 0.63 in determining HTN, HTN + AS, and MVD. In conclusion, higher choline levels were associated with increased risk of HTN and artery stenosis in hypertensive patients., (© 2020 Wiley Periodicals LLC.)

Hippophae rhamnoides subsp. Sinensis is a famous traditional medicinal plant in Tibet and Mongolia of China. Three novel flavonoid glycosides and ten known analogues were obtained from the seeds of H. rhamnoides. The structures of new compounds were elucidated by spectroscopics, chemical methods as well as literature data. In vitro assay, compounds 5-9, kaempferol and 70% ethanolic elution fraction showed prominent α-glucosidase inhibitory activities with IC 50 values ranging from 8.30 to 112.11 μM, better than that of the positive control, acarbose, whose IC 50 value was 1727.07 μM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: We investigated risk and prognostic factors for second primary squamous cell carcinoma (SCC) in patients with nasopharyngeal carcinoma (NPC) after radiotherapy (RT)., Methods: A total of 49 021 patients with NPC were treated at Sun Yat-Sen Cancer Center between January 1970 and December 2009. The incidence and management of second primary SCCs were analyzed., Results: A total of 142 patients (0.29%) developed second primary SCC, with 78.2% in the upper aerodigestive tract. Older age, smoking, and chemotherapy were associated with an increased rate of second primary SCC. The 3, 5, and 10-year overall survival (OS) rates for second primary SCC were 47.18%, 31.69%, and 11.97%, respectively. Advanced age, family history of cancer, and treatment modality were independent prognostic factors for survival., Conclusion: Second primary tumors rarely develop in patients with NPC treated with RT, but when this occurs, second primary SCC comprises a majority of these. Intensity-modulated RT may shorten the latency to second primary SCC. Surgery as the first-line treatment may improve survival and prognosis., (© 2018 Wiley Periodicals, Inc.)

Objective: To investigate the distribution of aldose reductase (AR) C-106T genetic polymorphism in Chinese Han population and its association with the risk for essential hypertension (EH)., Methods: The AR C-106T polymorphism was genotyped in 148 Chinese EH patients and 137 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The genotype distribution between groups was contrasted by Χ(2)- test and the degree of genetic association was evaluated by 95% confidence interval (CI)., Results: Frequency of the variant AR C-106T allele was 13.9% (95% CI: 11.2%-16.6%) in the controls, which was significantly lower than that in the Japanese (18.4% in 712 individuals, P=0.0063), the Australians (37.9% in 240 individuals, P<0.0001) and the Brazilians (34.7% in 62 individuals, P<0.0001). The frequency of AR C-106T allele was 11.7% (95% CI: 7.9%-15.5%) in the EH patients. No significant difference in the allele frequency was observed between the EH patients and the controls (P=0.147)., Conclusion: There is obvious racial difference in the distribution of AR C-106T polymorphism. The polymorphism is not associated with the risk for EH.

Background: Cytochrome P450 (CYP) oxidoreductase (POR) is the electron donor for microsomal CYP enzymes. The POR Ala503Val (POR*28 C > T) polymorphism has been reported to influence CYP3A activity in vivo in a white population. The influence of this polymorphism on CYP3A activity in vivo in the Chinese population currently unknown., Objective: This study was designed to assess the influence of the POR*28 polymorphism on the CYP3A activity in vivo in healthy Chinese men using midazolam (MID) as a probe drug., Methods: The POR*28 polymorphism was genotyped in healthy Chinese men. A randomized, 2-phase, open-label, crossover study was performed to assess in vivo CYP3A activity after both oral and intravenous MID administration, which reflect both intestinal and hepatic CYP3A or only hepatic CYP3A activity, respectively. The plasma concentrations of MID and 1-hydroxy-midazolam (1-OH-MID) were determined by liquid chromatography-tandem mass spectrometry., Results: A total of 73 healthy Chinese men were enrolled (CC genotype, 21 subjects; TT genotype, 11; CT genotype, 41), 22 of whom were selected for additional phenotyping of the CYP3A5*3 polymorphism (CC, 7; TT, 8; CT, 7). The mean (range) age, weight, height, and body mass index of the 22 subjects were 23 (20-28) years, 65.0 (57-75) kg, 1.74 (1.63-1.80) m, and 22.01 (19.27-24.46) kg/m(2), respectively. The frequency of the POR*28 T (503V) allele was 43.2%. No significant differences in the demographic characteristics of the subjects were observed between the POR*28 genotype groups. All of the POR*28 CC and TT homozygotes and 2 of the POR*28 CT heterozygotes carried the CYP3A5*3/*3 genotype (CYP3A5 low expressors); 6 CT heterozygotes carried the CYP3A5*1 allele (CYP3A5 expressors). The mean (SD) 1-OH-MID AUC(0-8) was significantly greater in the TT homozygotes compared with the CT heterozygotes after intravenous (86.15 [24.34] vs 53.21 [31.36] ng/mL/h; P = 0.026) but not oral (126.36 [31.60] vs 103.09 [31.00] ng/mL/h; P = 0.159) MID administration. Mean 1-OH-MID C(max) was significantly greater in the TT homozygotes (51.40 [10.72] ng/mL) compared with the CC homozygotes (31.47 [11.54] ng/mL; P = 0.002) and CT heterozygotes (30.12 [9.21] ng/mL; P = 0.001) after intravenous MID administration. After intravenous MID injection, the MID metabolic ratio was significantly greater in the TT homozygotes compared with carriers of the C allele (P = 0.031). Based on these findings, no significantly differences in overall (hepatic plus intestinal) CYP3A in vivo activity were observed between the POR*28 genotypes., Conclusion: These findings suggest that individuals with the POR*28 C > T polymorphism underwent an increase in 1-hydroxylation of MID after intravenous MID administration, and that the polymorphism was associated with increased hepatic, but not intestinal, CYP3A activity in these healthy Chinese volunteers., (Crown Copyright © 2011. Published by EM Inc USA. All rights reserved.)

The objective of this study was to evaluate whether elective neck dissection could improve regional control or survival time in clinical stage I squamous cell carcinoma of the oral tongue (OTSCC). This was a retrospective study of patients with surgical treatment between January 1991 and December 2003. A total of 131 patients were included in the study, and all of them received operation of the primary site, while 88 cases underwent selective neck dissection simultaneously including level I-III neck dissection in 49 patients and level I-V neck dissection in 39 patients. In all these cases, the rate of occult neck metastases was 23.7%. The 4-year local control rates in patients with only primary site treatment, patients with level I-III neck dissection and patients with level I-V neck dissection were 81.0%, 83.6% and 89.1%, respectively. By univariate analyse, neck dissection did not increase regional control rate, disease free survival (DFS) or overall survival (OS). Multivariate analyses showed that neck dissection was not an independent factor for DFS or OS. This study showed that the occult neck metastases rate was 23.7% in clinical stage I OTSCC. Elective neck dissection did not significantly improve regional control, DFS and OS in clinical stage I patients. There is a need for accurate and valid methods to select the patients who would benefit from elective neck treatment., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Chinese-descent rhesus macaques have become more prevalent for HIV infection and vaccine investigation than Indian-origin macaques. Most of the currently available data and reagents such as major histocompatibility complex (MHC) class I tetramers, however, were derived from Indian-origin macaques due to the dominant use of these animals in history. Although there are significant differences in the immunogenetic background between the two macaque populations, they share a few of common MHC class I alleles. We reported in this study the procedure for preparation of a soluble Mamu-B*1703 (a MHC class I molecule of Chinese macaques) monomer and tetramer loaded with a dominant simian immunodeficiency virus (SIV) epitope IW9 (IRYPKTFGW) that was identified to be Mamu-B*1701-restricted in Indian macaques. The DNA fragment encoding the Mamu-B*1703 extracellular domain fused with a BirA substrate peptide (BSP) was amplified from a previously cloned cDNA and inserted into a prokaratic expression vector. In the presence of the antigenic peptide IW9 and light chain beta2-microglobulin, the expressed heavy chain was refolded into a soluble monomer. After biotinylation, four monomers were polymerized as a tetramer by phycoerythrin-conjugated streptavidin. The tetramer, having been confirmed to have the right conformation, was a potential tool for investigation of antigen-specific CD8(+) T-lymphocytes in SIV vaccine models of Chinese macaques. And our results also suggested that some antigenic peptides reported in Indian-origin macaques could be directly recruited as ligands for construction of Chinese macaque MHC tetramers.