Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

ObjectiveTo observe the clinical effectiveness and safety of Dingchan Granule （定颤颗粒） for paroxysmal atrial fibrillation with syndrome of qi stagnation and blood stasis. MethodsUsing a randomised， double-blind， placebo controlled study method， 90 patients with paroxysmal atrial fibrillation with qi stagnation and blood stasis syndrome were divided into 45 cases each in the treatment group and the control group. Both groups were given conventional western medicine treatment， and the treatment group was additionally treated with Dingchan Granule， while the control group was treated with Dingchan Granule placebo， both of which were taken orally for 8 g each time twice a day. Both groups were treated for 8 weeks. We compared the clinical effectiveness， the improvement of traditional Chinese medicine （TCM） symptoms and the recovery rate of atrial fibrillation between the two groups. We compared the number and duration of atrial fibrillation episodes， TCM symptoms score， atrial fibrillation symptom classification， 24-hour average ventricular rate， Pittsburgh Sleep Quality Index （PSQI）， anxiety index， depression index before and after treatment， and evaluated the safety of the two groups. ResultsThe total clinical effectiveness rate in the treatment group was 82.22% （37/45）， which was better than 60.00% （27/45） in the control group （P＜0.05）. The total effective rate of TCM syndrome effectiveness in the treatment group was 88.89% （40/45）， which was better than 66.67% （30/45） in the control group （P＜0.05）； and the rate of atrial fibrillation regression in the treatment group was 26.67% （12/45）， better than 6.67% （3/45） in the control group （P＜0.05）. The number and duration of atrial fibrillation episodes in both groups were significantly decreased （P＜0.01）， and the number and duration of atrial fibrillation episodes in the treatment group were lower than those in the control group （P＜0.01）. The TCM syndrome scores of both groups after treatment were significantly lower than before treatment （P＜0.01）， and the scores of the treatment group was lower than those of the control group （P＜0.05）. The severity of atrial fibrillation symptoms and the grading of atrial fibrillation symptoms in both groups after treatment were improved （P＜0.01）， and the degree of symptom improvement in the treatment group was better than that in the control group （P＜0.01）. The 24-hour average ventricular rate of both groups after treatment was significantly lower （P＜0.01）. The PSQI， anxiety index and depression index of the treatment group were all lower than before treatment （P＜0.01）， while the PSQI and anxiety index of the control group were both lower than before treatment （P＜0.01 or P＜0.05）， the PSQI， anxiety index and depression index of the treatment group being lower than those of the control group （P＜0.05 or P＜0.01）. No adverse events occurred in both groups， and no abnormalities were observed in blood， urine， stool routine， liver and kidney function， and coagulation function indexes. ConclusionDingchan Granule for paroxysmal atrial fibrillation with qi stagnation and blood stasis syndrome can alleviate clinical symptom， improve TCM symptom scores， increase atrial fibrillation recovery rate， stabilise the average ventricular rate， and significantly improve the quality of sleep， alleviate the anxiety and depression， with a good safety profile.

Objective: We employed Mendelian randomization (MR) to test the traditional Chinese medicine (TCM) theory of emotional pathogenesis concept and explore the causal relationship between negative emotions and chronic obstructive pulmonary disease (COPD). Methods: Data of negative emotions, bronchitis, emphysema, and C-reactive protein (CRP) levels were downloaded from genome-wide association study (GWAS) public database for a two-sample MR analysis. Independent single-nucleotide polymorphisms (SNPs) associated with negative emotions, bronchitis, and emphysema were selected as instrumental variables. Primary causal estimates were derived using inverse-variance weighting (IVW), supplemented by weighted median (WM), and simple mode (SM) methods. Sensitivity analyses included MR-Egger regression and MR-PRESSO to assess pleiotropy, Cochran’s Q test for heterogeneity, and multivariate MR to adjust for smoking. Mediation analysis evaluated the role of inflammatory markers. Reverse MR was tested for bidirectional causality. Weak instrument bias was mitigated via F-statistic thresholds (> 10). All analyses were conducted in RStudio. Results: MR analysis identified significant causal effects of several negative emotions on COPD. Genetically, the IVW analysis of seen doctors for nerves anxiety tension or depression [ORIVW = 1.006, 95% CI = (1.002, 1.010), P = 0.002], sensitivity/hurt feelings [ORIVW = 1.024, 95% CI = (1.004, 1.044), P = 0.017], and irritability [ORIVW = 1.019, 95% CI = (1.003, 1.035), P = 0.019 were robustly associated with increased risks of COPD. No heterogeneity was detected among the different instrumental variables (IVs) for depression (P = 0.655) and irritability (P = 0.163). MR-Egger regression intercepts for all emotional exposures were close to zero and statistically non-significant, indicating no evidence of directional pleiotropy. The horizontal pleiotropy results showed that except for worry (MR-PRESSO P = 0.006), other emotion exposures confirming no substantial pleiotropic bias. Multivariable MR demonstrated that anxiety remained independently associated with COPD after adjusting for smoking (P = 0.002), while associations with other negative emotions were attenuated post-adjustment. The mediation analysis revealed that CRP mediated 3.93% of the total effect of anxiety on COPD. However, reverse MR analysis found no evidence of reverse causality. Conclusion This study confirmed the causal effects of negative emotions on COPD through MR analysis and revealed that negative emotions may trigger CRP production, which plays an essential mediating role in this relationship. This study provides a reliable modern theoretical basis for emotion theory in TCM.

Objective To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach.Methods The literature of forensic mixed stain included in the core col-lection of Web of Science database from 2011 to 2022 were collected as the study object,and the an-nual publication number,countrie(region),institution,journal,keywords,etc.were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software.Re-sults A total of 732 articles on forensic mixed stain were included from 2011 to 2022,with the an-nual number of articles published and the annual citation frequency showing a steady increase year by year.Among the 59 countries(regions)with the most published articles,the United States ranked first with 246 articles,followed by China with 153 articles.The literature came from 104 journals,and the total number of articles published in the top 10 journals was 633.FORENSIC SCI INT GENET ranked first with 307 articles.Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters,namely the genetic marker development group(blue),the mixed stain typing analysis theory group(red),the sequencing analysis group(yellow),and the case sample research group(green).It can be divided into four development stages in terms of different time peri-ods:early development(2011-2013),middle development(2014-2016),rapid development(2017-2020)and latest development(2021-2022).Conclusion The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend.Machine learning,next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years,which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.

Based on the theory of "one qi circulation" founded by HUANG Yuanyu， the core disease mechanism of colorectal cancer is the innate spleen deficiency and stomach qi failing to bear downward， which leads to the turbidity assemble in large intestine， forming the carcinoma toxin， and ultimately transforms into colorectal cancer. The treatment should base on recovering the circulation of qi， Huangya Decoction （黄芽汤） as the basic formula， the circulation of qi ascending and descending as the base， adjusting ascending and descending together with Xiaqi Decoction （下气汤）， and differentiating the syndrome on yin-yang excess-deficiency； for spleen-kidney yang deficiency syndrome， treated with Tianhun Decoction （天魂汤） to supplement liver， kidney and assist yang； for liver-kidney yin deficiency syndrome， treated wtih Dipo Decoction （地魄汤） to supplement lung， kidney， and assist yang. They jointly prompt one qi circulation to provide the thoughts for the treatment of colorectal cancer by traditional Chinese medicine.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin apioside,alibiflorin,swertiamarin,methyl gallate,benzoylpaeoniflorin,sweroside,6′-O-β-D-glucosylgentiopicroside,isoliquiritigenin,loganic acid,liquiritigenin,gallic acid,paeoniflorin,oxypaeoniflorin,gentiopicroside,glycyrrhizic acid,isoliquiritoside and liquiritin in Yangxue Ruanjian Capsules.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18column(2.1 mm×100 mm,1.7 μm),with the mobile phase comprising of 2 mmol/L ammonium acetate(containing 0.1%formic acid)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Seventeen constituents showed good linear relationships within their own ranges(r>0.999 6),whose average recoveries were 91.33%-104.03%with the RSDs of 1.58%-3.50%.CONCLUSION This rapid,accurate and stable method can be used for the quality control of Yangxue Ruanjian Capsules.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To explore the effects of panobinostat on the proliferation,migration and invasion of renal carcinoma cells via targeting ADP ribosylated factor-like protein 4C(ARL4C).Methods According to different treatments,human renal carinoma 786-O cells were divided into blank group(phosphate buffer treatment),experimental group(50 nmol·L-1 panobinostat treatment),empty vector group(transfection with empty vector and no treatment),overexpression group(transfection with ARL4C overexpression vector and no treatment)and combined group(transfection with ARL4C overexpression vector and 50 nmol·L-1 panobinostat treatment).The proliferation,migration and invasion of cells were detected by methyl thiazolyl tetrazolium assay and scratch assay.Cholesterol transport levels in cells were detected by enzyme-labeled assay.The mRNA and protein levels of ARL4C in cells were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot.Results The indicators of cell proliferation in blank group,experimental group,empty vector group,overexpression group and combined group were(100.00±0)％,(61.08±5.82)％,(101.22±5.92)％,(121.94±6.63)％and(101.78±6.87)％;the indicators of cell migration were(44.59±2.49)％,(29.02±2.09)％,(42.75±2.42)％,(54.19±3.05)％and(41.91±2.75)％;the indicators of cell invasion were 264.50±6.52,182.70±5.83,257.80±7.91,322.40±8.27 and 266.80±8.15;the intracellular levels of cholesterol were(72.48±6.21),(36.48±3.44),(73.89±5.91),(89.21±8.89)and(73.06±6.92)mmol·L-1;the relative expression levels of ARL4C mRNA were 1.23±0.22,0.24±0.08,1.27±0.25,1.67±0.38 and 1.27±0.25;the relative expression levels of ARL4C protein were 1.06±0.03,0.17±0.04,1.03±0.05,1.37±0.18 and 1.05±0.08,respectively.Between the blank group and experimental group,the above indicators have statistically significant differences(all P＜0.05);compared with the blank group and empty vector group,the above indicators in overexpression group have statistically significant differences(all P＜0.05).Conclusion Panobinostat downregulate the intracellular levels of cholesterol by reducing the expression level of ARL4C in 786-O cells,thus inhibiting the proliferation,migration and invasion of renal carcinoma cells.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD+)levels and nabothian cysts.This study aimed to assess the association between NAD+levels and nabothian cysts in healthy Chinese women. Methods Multivariate logistic regression analysis was performed to analyze the association between NAD+levels and nabothian cysts. Results The mean age was 43.0±11.5 years,and the mean level of NAD+was 31.3±5.3 μmol/L.Nabothian cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and 84(12.6%)participants,respectively.The total nabothian cyst prevalence gradually decreased from 37.4%to 21.6%from Q1 to Q4 of NAD+and the prevalence of single and multiple nabothian cysts also decreased across the NAD+quartiles.As compared with the highest NAD+quartile(≥34.4 μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD+Q1 was 1.89(1.14-3.14)for total nabothian cysts.The risk of total and single nabothian cysts linearly decreased with increasing NAD+levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD+levels of 28.0 to 35.0 μmol/L. Conclusion:Low NAD+levels were associated with an increased risk of total and multiple nabothian cysts.