Di'ao Xinxuekang activates IRS-1/PI3K/Akt signal pathway to improve insulin resistance in nonalcoholic fatty hepatitis mice / 中国临床药理学与治疗学

AIM: To study the effect and mechanism of Di'ao Xinxuekang (DXXK) on insulin resistance in nonalcoholic steatohepatitis (NASH) mice. METHODS: C57BL/6J mice were randomly divided into normal group and model group. After 16 weeks of high-fat diet, the model group was randomly divided into model group and Pioglitazone group (6.0 mg · kg

Literature analysis of ADR after the listing of apatinib / 中国药房

OBJECTIVE To explore the characteristics and regulations of adverse drug reactions （ADR） caused by apatinib， and to provide a reference for the safe use of apatinib in clinic. METHODS Case and group reports on ADR and safety evaluation of apatinib were retrieved from Chinese and English databases such as CNKI， Wanfang medical network， VIP and PubMed since its listing in 2014， literature data were extracted and statistically analyzed after screening. RESULTS Totally 101 cases were included， involving 221 ADR. In the above cases， the male-to-female ratio was 1.24∶1， with the highest proportion of patients aged 51 to 70 years， most of the patients were given a dose of 500 mg or more， and the patients given low dose of apatinib combined with other antitumor drugs were also likely to have ADR. One to two types of adverse reaction were the most common， while the types could reach up to six. Most ADR occurred within 30 days after medication， and the systems/organs involved were mainly the cardiovascular system damage，skin and its accessories damage， gastrointestinal system damage and urinary system damage； the main clinical manifestations were hypertension/aggravation，hand-foot syndrome，abdominal pain diarrhea and albuminuria， etc. Hypertension/aggravation， hand-foot syndrome and myelosuppression were the most common serious ADR. Most ADR could be improved/cured by suspension of administration， dose downregulation and symptomatic treatment. All 4 patients who died had underlying diseases， and their ECOG scores all ≥2 points. Special ADR （such as reversible posterior encephalopathy syndrome， psychiatric disorders， and cognitive impairment） were mostly caused by apatinib itself， or may be caused by apatinib in combination with the primary or underlying disease. CONCLUSIONS Advanced age， large dose， combination medication， underlying diseases and poor physical condition might be the high risks for ADR caused by apatinib. It is recommended to monitor the blood pressure，urine protein and skin of hands and feet of all patients with medication on a daily basis，pay attention to the occurrence of special ADR， and timely detect abnormal states and give effective intervention，so as to avoid the aggravation of ADR and other secondary ADR.

Association of polycyclic aromatic hydrocarbon metabolite concentration with sleep quality in workers / 环境与职业医学

Background Sleep is a crucial physiological activity for the human body, and research has shown that air pollution can affect sleep quality. However, the association between polycyclic aromatic hydrocarbons (PAHs) exposure, neurotoxic compounds in air pollutants, and sleep quality remains uncertain. Objective To evaluate the association of PAHs exposure with sleep quality, and to provide evidence for improving sleep quality. Methods This study used a cross-sectional design. We selected 632 workers from a coking plant of a large state-owned enterprise as the exposure group, and 477 workers from the energy and power plant of the same enterprise as the control group. All workers worked in three shifts. A questionnaire survey was conducted to collect basic information including gender, years of service, age, educational level, smoking, alcohol consumption, consumption of fried foods, cooking frequency, types of cooking fuels. Worker's post-shift morning midstream urine was sampled to determine the concentrations of eight PAHs metabolites (OH-PAHs) using gas chromatography-tandem mass spectrometry (GC-MS). Worker's sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI). A higher PSQI score indicated a lower sleep quality. Associations of urinary OH-PAHs levels with sleep quality in the workers were analyzed using linear regression, Bayesian kernel-machine regression (BKMR), and quantile g-computation. Results The median (P25, P75) concentration of total OH-PAHs in the exposure group [88.84 (46.27, 151.96) μg·L−1] was higher than that in the control group [54.33 (24.86, 97.97) μg·L−1]. Additionally, the PSQI score (\begin{document}$ \overline{x}\pm {s} $\end{document}) in the exposure group (5.16±3.84) was higher than that in the control group (4.60±3.17). The multiple linear regression revealed that an increase in the sum of the concentrations of eight OH-PAHs after natural logarithmic transformation (lnΣ8OH-PAHs) was associated with an increase of 0.3646 (95%CI: 0.1337, 0.5955) in PSQI score, and an increase in lnΣlow-ring OH-PAHs was associated with an increase of 0.2954 (95%CI: 0.0941, 0.4967) in PSQI score. The BKMR analysis demonstrated that PSQI score was gradually increased as the increasing of lnΣ8OH-PAHs concentration. The quantile g-computation analysis indicated that a quantile increase in lnΣ8OH-PAHs concentration was associated with an increase of 0.4062% (95%CI: 0.1176%, 0.6949%) in PSQI score. Conclusion Compared to the controls, the coking workers show a higher concentration of urinary OH-PAHs and report worse sleep quality. The concentration of OH-PAHs is significantly negatively associated with sleep quality.

Comparing the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia in preterm infants / 中华儿科杂志

Objective: To compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks. Methods: The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children's Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria. Results: The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria (Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria (Z=0.02, P=0.984). Conclusion: The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.

Effects and mechanism of polysaccharides from Hedyotis diffusa on isoniazid-induced liver injury / 中国药房

OBJECTIVE To investigate the effects and mechanism of polysaccharides from Hedyotis diffusa （HDP） on isoniazid （INH）-induced liver injury. METHODS Healthy transgenic zebrafish with liver-specific fluorescence were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+50 mg/mL HDP） and HDP high- concentration group （4 mmol/L INH+100 mg/mL HDP）. After grouping treating， the liver fluorescence area， fluorescence intensity and pathological changes of liver tissue were observed. Human liver L02 cells were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+2 mg/mL HDP）， and HDP high-concentration group （4 mmol/L INH + 4 mg/mL HDP）. After grouping treating， the cell viability was detected， and the levels of alanine transaminase （ALT）， aspartate transaminase （AST）， and the content of glutathione （GSH） as well as the expression levels of silent information regulator 1 （Sirt1）， nuclear factor-erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1） and quinone oxidoreductase 1 （NQO1） proteins were detected. RESULTS Compared with the model group， the HDP low- and high-concentration groups showed varying degrees of increase in the fluorescence area and fluorescence intensity （except for HDP low-concentration group） of zebrafish liver （P＜0.05 or P＜0.01）， and the characteristics of liver injury and necrosis had been improved to varying degrees. Compared with model group， the survival rate of L02 cells， the content of GSH （except for HDP low-concentration group）， the protein expression levels of Sirt1 （except for HDP low-concentration group）， Nrf2， NQO1， HO-1 （except for HDP low-concentration group） were significantly increased in HDP low- and high-concentration groups （P＜0.05 or P＜0.01）， and the levels of ALT and AST （except for HDP low-concentration group） were significantly decreased （P＜0.05）； the number of survival cells significantly increased， while the number of damaged or dead cells significantly decreased. CONCLUSIONS HDP has a potential protective effect against INH-induced liver injury， the mechanism of which may be associated with activating Sirt1/Nrf2 signaling pathway， improving mitochondrial function and enhancing antioxidant capacity.

Total Saponins of Dioscorea Mitigate Nonalcoholic Steatohepatitis in Mice by Regulating AMPK/SREBP-1c/ACC Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the role and mechanism of total saponins of Dioscorea （TSD） in mitigating nonalcoholic steatohepatitis （NASH） in mice. MethodForty-eight C57BL/6J mice were randomized into a normal group and a modeling group. The mice for modeling were fed with a high-fat and high-cholesterol diet + 20% fructose solution for 16 weeks and randomized into model， atorvastatin （4 mg·kg-1·d-1）， and high-， medium-， and low-dose （200， 60， and 20 mg·kg-1·d-1） TSD groups. The mice were administrated with corresponding doses of drugs by gavage for 8 weeks. The mouse activity， liver index， levels of total cholesterol （TC）， triglycerides （TG）， and free fatty acids （FFAs） in the liver， and levels of TC， TG， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， γ-glutamyl transferase （GGT）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the serum were measured. Hematoxylin-eosin staining， Masson staining， oil red O staining， and transmission electron microscopy were employed to observe the pathological changes， lipid accumulation， and morphological changes of liver ultrastructure. Western blot was employed to determine the protein levels of AMP-activated protein kinase （AMPK）， sterol regulatory element-binding protein-1c （SREBP-1c）， acetyl-CoA carboxylase （ACC）， and phosphorylated ACC （p-ACC） in the liver tissue. ResultCompared with the normal group, the activity of mice in the model group decreased(P<0.05， P<0.01), the levels of TC, TG, FFA and serum TC, TG, ALT, AST, GGT, IL-1β and TNF-α, liver coefficient and liver pathology scores were significantly increased, the expression of p-AMPK/AMPK and p-ACC proteins in liver tissues was significantly reduced, and the expressions of SREBP-1c and ACC proteins were significantly increased (P<0.01). Compared with the model group， atorvastatin increased the mouse activity （P<0.05）， while each dose of TSD caused no significant changed in the mouse activity. The levels of TC, TG, FFA in liver and serum TC, TG, ALT, AST, GGT, IL-1β, TNF-α, liver coefficient and liver pathological score in TSD and atorvastatin groups were significantly decreased, and the expressions of p-AMPK/AMPK and p-ACC in liver tissue were significantly increased. The expressions of SREBP-1c and ACC were significantly decreased (P<0.05,P<0.01). ConclusionTSD may alleviate NASH in mice by regulating the AMPK/SREBP-1c/ACC signaling pathway to reduce lipid synthesis.

Advances in research on treatment of tympanosclerosis / 临床耳鼻咽喉头颈外科杂志

Tympanosclerosis is the hyaline degeneration and calcium deposition of the lamina propria of tympanic membrane and the submucosa of middle ear under long-term chronic inflammatory stimulation. At present, treatment primarily involves the surgical removal of sclerotic foci and reconstruction of auditory ossicular chain. However, excision of sclerotic lesions near critical structures like the facial nerve canal and vestibular window may result in complications like facial paralysis, vertigo, and sensorineural hearing loss. Developing safer and more effective treatments for tympanosclerosis has become an international research focus. Recent years have seen novel explorations in the treatment of tympanosclerosis. Therefore, this article reviews the latest advancements in research on the treatment of tympanosclerosis.

Specific DNA barcodes screening, germplasm resource identification, and genetic diversity analysis of Platycodon grandiflorum / 药学学报

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Clinical feature and genetic analysis of a patient with Idiopathic hypogonadotropic hypogonadism due to a novel variant of CHD7 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical feature and genetic etiology of a patient with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) due to variant of CHD7 gene.@*METHODS@#A patient who had presented at Anhui Provincial Children's Hospital in October 2022 was selected as the study subject. Clinical data of the patient was collected. The patient and his parents were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The patient had featured delayed development of secondary sexual characteristics but normal olfactory function. Genetic testing revealed that he has harbored a c.3052C>T (p.Pro1018Ser) missense variant of the CHD7 gene, for which both of his parents were of the wild type. The variant has not been recorded in the PubMed and HGMD databases. Analysis of amino acid sequences suggested that the variant site is highly conserved, and the variant may affect the stability of protein structure. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.3032C>T variant was classified as a likely pathogenic (PS2+PM2_Supporting+PP2+PP3+PP4).@*CONCLUSION@#The delayed development of secondary sexual characteristics of the patient may be attributed to the c.3052C>T (p.Pro1018Ser) variant of the CHD7 gene. Above finding has expanded the variation spectrum of the CHD7 gene.

Intelligent Electrocardiogram Analysis in Medicine: Data, Methods, and Applications / 中国医学科学杂志(英文版)

Electrocardiogram (ECG) is a low-cost, simple, fast, and non-invasive test. It can reflect the heart's electrical activity and provide valuable diagnostic clues about the health of the entire body. Therefore, ECG has been widely used in various biomedical applications such as arrhythmia detection, disease-specific detection, mortality prediction, and biometric recognition. In recent years, ECG-related studies have been carried out using a variety of publicly available datasets, with many differences in the datasets used, data preprocessing methods, targeted challenges, and modeling and analysis techniques. Here we systematically summarize and analyze the ECG-based automatic analysis methods and applications. Specifically, we first reviewed 22 commonly used ECG public datasets and provided an overview of data preprocessing processes. Then we described some of the most widely used applications of ECG signals and analyzed the advanced methods involved in these applications. Finally, we elucidated some of the challenges in ECG analysis and provided suggestions for further research.

A Nested Case-Control Study to Explore the Association between Immunoglobulin G N-glycans and Ischemic Stroke / 生物医学与环境科学（英文）

OBJECTIVE@#This study prospectively investigates the association between immunoglobulin G (IgG) N-glycan traits and ischemic stroke (IS) risk.@*METHODS@#A nested case-control study was conducted in the China suboptimal health cohort study, which recruited 4,313 individuals in 2013-2014. Cases were identified as patients diagnosed with IS, and controls were 1:1 matched by age and sex with cases. IgG N-glycans in baseline plasma samples were analyzed.@*RESULTS@#A total of 99 IS cases and 99 controls were included, and 24 directly measured glycan peaks (GPs) were separated from IgG N-glycans. In directly measured GPs, GP4, GP9, GP21, GP22, GP23, and GP24 were associated with the risk of IS in men after adjusting for age, waist and hip circumference, obesity, diabetes, hypertension, and dyslipidemia. Derived glycan traits representing decreased galactosylation and sialylation were associated with IS in men (FBG2S2/(FBG2 + FBG2S1 + FBG2S2): odds ratio ( OR) = 0.92, 95% confidence interval ( CI): 0.87-0.97; G1 n: OR = 0.74, 95% CI: 0.63-0.87; G0 n: OR = 1.12, 95% CI: 1.03-1.22). However, these associations were not found among women.@*CONCLUSION@#This study validated that altered IgG N-glycan traits were associated with incident IS in men, suggesting that sex discrepancies might exist in these associations.

Analysis of conjunctival sac microflora and antibiotic susceptibility testing in adolescents after wearing orthokeratology lens / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the bacterial flora and antibiotic susceptibility testing of conjunctival sac in adolescents after wearing orthokeratology(OK)lens.METHODS:A total of 101 adolescents aged 8 to 14 who admitted to outpatient department of Xi'an No.1 Hospital from September 2021 to August 2022 were recruited in this cross-sectional observational study. There were 51 cases wearing OK Lens(wearing group)and 50 patients not wearing contact lens(non-lens group), the right eye of all patients was selected into the group. The culture of bacterial flora in conjunctival sac between the two groups were compared, the species were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the antibiotic susceptibility testing was carried out for the positive strains cultured in the wearing group.RESULTS:The positive rate of conjunctival sac bacterial cultured in the wearing group and the non-lens group was 68.6%(35/51)and 60.0%(30/50), respectively(P&#x003E;0.05). In both groups, the bacteria with the highest detection rate were staphylococcus epidermidis and staphylococcus aureus. The sensitivity rates of the strains detected in the wearing group to drugs are as follows: Levofloxacin(98%), Moxifloxacin(98%), Gatifloxacin(98%), Cefuroxime(98%), Cefathiamidine(98%), Rifampicin(98%), Chloramphenicol(96%), Cefoxitin(95%), Clindamycin(80%), Gentamicin(74%), Fusidic acid(72%), Tobramycin(64%), Compound sulfamethoxazole(26%), Mezlocillin(10%), Azithromycin(6%), of which the sensitivity rate of Gram-positive cocci was 100% sensitive to Vancomycin.CONCLUSION:Gram-positive cocci are the main bacteria isolated from conjunctival sac of adolescents after wearing OK Lens. Wearing OK Lens will not significantly increase the positive rate of conjunctival sac bacterial flora. Results of antibiotic susceptibility testing may provide guidance for empirical medication in patients wearing OK lens after eye infection.

Concomitant repair of moderate or less tricuspid regurgitation during mitral valve surgery improves early and mid-term prognosis of tricuspid valve and right heart function / 中国胸心血管外科临床杂志

@#Objective    To investigate the effect of concomitant tricuspid valve repair during mitral valve surgery on the early and mid-term prognosis of the tricuspid valve and right heart function in the patients with moderate or less tricuspid regurgitation. Methods    A retrospective study of 461 patients with mitral valve disease requiring cardiac surgery combined with moderate or less tricuspid regurgitation in our hospital from 2011 to 2014 was done. They were 309 males and 152 females with a median age of 53.00 (44.00, 60.00) years. According to whether they received tricuspid valve repair (Kay’s annuloplasty, DeVega’s annuloplasty or annular ring implantation), the patients were divided into a mitral valve surgery only group (a nTAP group, n=289) and a concomitant tricuspid valve repair group (a TAP group, n=172). At the same time, 43 patients whose tricuspid valve annulus diameter was less than 40 mm in the TAP group were analyzed in subgroups. Results    The median follow-up duration was 3.00 years (range from 0.10 to 9.30 years). There was no perioperative death. Three months after surgery, the anteroposterior diameter of the right ventricle in the TAP group was significantly improved compared with that in the nTAP group [–1.00 (–3.00, 1.00) mm vs. 0.00 (–0.20, 2.00) mm, P=0.048]. Three years after surgery, the improvement of right ventricular anteroposterior diameter in the TAP group was still significant compared with the nTAP group [–1.00 (–2.75, 2.00) mm vs. 2.00 (–0.75, 4.00) mm, P=0.014], and the patients in the TAP group were less likely to develop moderate or more tricuspid regurgitation (3.64% vs. 35.64%, P<0.001). Annuloplasty ring implantation was more effective in preventing regurgitation progression (P=0.044). For patients with a tricuspid annulus diameter less than 40 mm, concomitant tricuspid valve repair was still effective in improving the anteroposterior diameter of the right ventricle in the early follow-up (P=0.036). Conclusion     Concomitant tricuspid valve repair for patients with moderate or less tricuspid regurgitation during mitral valve surgery can effectively improve the tricuspid valve and right heart function in the early and mid-term after surgery. Annuloplasty ring implantation is more effective in preventing regurgitation progression. Patients whose tricuspid annulus diameter is less than 40 mm can also benefit from concomitant tricuspid repair.

Synthesis and anti-HCC activity of full 2ʹ-F/OMe-siRNA encapsulated with neutral cytidinyl/cationic lipid / 药学学报

A variety of full 2ʹ-F/OMe-modified siRNAs were designed and synthesized, and the activity against hepatocellular carcinoma Huh-7 and HepG2 cells was evaluated. K&A DNA/RNA H-8 synthesizer was used to synthesize siRNAs, and neutral cytidinyl lipid DNCA mixed with cationic lipid CLD were used to transfect siRNA. By RT-qPCR and CCK-8 assay, the target gene silence and the proliferation of Huh-7 and HepG2 cells were detected. The siRNAs loading into Ago2 protein was detected by RNA-binding protein immunoprecipitation. Drug uptake and cell apoptosis were detected by flow cytometry, and the expression of PLK1 protein was detected by Western blot. Partial full 2ʹ-F/OMe modified siRNAs, especial siPLK1A3, increased the uptake of Huh-7 cells, enhanced their binding to Ago2 and gene silencing activity, down-regulated PLK1 protein, as well as induced more Huh-7 cell apoptosis and proliferation inhibition activity. It provides important data for the development of novel siRNA modification patterns and anti-HCC formulations.

Screening of specific DNA barcode, identification of germplasm resources, and analysis of genetic diversity of Atractylodes chinenesis / 药学学报

italic>Atractylodes chinensis has important medicinal and economic values. In this study, the chloroplast genome sequences of four A. chinensis samples from different producing areas were sequenced using the Illumina platform. The specific DNA barcodes were screened and the germplasm resources of A. chinensis samples from different producing areas and the genetic diversity of the population were analyzed basing on the specific barcodes. The whole chloroplast genomes of the four A. chinensis samples had a typical cyclic tetrad structure, with 112 genes annotated. The comparative genomics results indicated that ccsA and trnC-GCA_petN were potential specific DNA barcodes for intraspecific identification of A. chinensis. Polymerase chain reaction (PCR) analysis of ccsA and trnC-GCA_petN was performed on 256 samples from 14 areas in 9 provinces, and the amplification efficiency was 100%. Sequence analysis showed that ccsA and trnC-GCA_petN had 11 and 22 variant positions, which could identify 16 and 22 haplotypes, respectively. The combined sequence analysis identified 39 haplotypes, named Hap1-Hap39, of which the most abundant and widely distributed genotype was Hap9. Haplotype diversity (Hd) = 0.896 and nucleotide diversity (Pi) = 0.002 22 indicated high genetic diversity at the species level in A. chinensis. The genetic distances of the haplotypes were 0.000 00-0.004 88, indicating that there were small genetic differences among the haplotypes. The results of phylogenetic tree analysis showed that 39 haplotypes had very close genetic relationship, and formed two obvious branches with other groups of the same genus except Atractylodes macrocephala. This study plays an important role in the identification of the origin of A. chinensis and the protection and breeding of germplasm resources.

Analysis of Fusarium oxysporum infection on changes of Astragalus metabolism by metabolomic approach / 药学学报

italic>Astragalus is a commonly used Chinese medicinal material in traditional Chinese medicine (TCM), and with the increase of planting area in recent years, the damage of Astragalus root rot has worsened year by year, which seriously affecting its quality and yield. Fusarium oxysporum is one of the main pathogens causing root rot in astragalus. In this study, UPLC-Q-TOF-MS based metabolomic approach combined with multivariate statistical analysis were used to analyze the metabolite changes of Astragalus in response to F. oxysporum infection. The results showed that 62 metabolites in the Astragalus had significant changes after inoculation of F. oxysporum. Polar metabolites included 40 flavonoids, 8 saponins, 2 nucleosides, 1 vitamin, 1 organic acid, 1 amino acid; while lipid metabolites included 3 fatty acids, 1 diradylglycerols, 2 lysophosphatidylcholine, 1 lysophosphatidylglycerol, 1 phosphatidylinositol, 1 sterol lipid. Among these differential metabolites, the relative content of flavonoids, vitamin B2, tryptophan and salicylic acid were increased, while the relative content of saponins were decreased. Correlation analysis showed that the flavonoids were positively correlated with each other, and positively correlated with most lipids, but negatively correlated with most saponins. In addition, studies have shown that F. oxysporum infection is not an influencing factor for the generation of malonyl substitution of flavonoid. This study elucidates the effect of F. oxysporum infection on Astragalus from the perspective of plant metabolism, which provides a basis for exploring the interaction mechanism between the Astragalus and F. oxysporum and further promoting molecular breeding.

Diagnosis and treatment of acute kidney injury after liver transplantation / 器官移植

Acute kidney injury is a common complication after liver transplantation, which severely affects clinical prognosis of liver transplant recipients. Multiple factors before, during and after liver transplantation may cause kidney injury. If not properly treated, it may progress into chronic kidney diseases, which significantly increases postoperative fatality and negatively affects clinical efficacy of liver transplantation. Therefore, prevention, diagnosis and treatment of acute kidney injury after liver transplantation is a hot topic for clinicians. In this article, the definition, diagnosis, risk factors, prevention and treatment of acute kidney injury after liver transplantation were reviewed, and potential risk factors and related therapeutic strategies during different stages of acute kidney injury after liver transplantation were analyzed, aiming to lower the risk of acute kidney injury after liver transplantation and further improve clinical prognosis of liver transplant recipients by optimizing treatment regimens.

Mechanism of Qingre Lishi Huazhuo Method（Modified Simiaosan） on Chronic Gouty Arthritis of Dampness-heat Obstruction Syndrome Based on NLRP3/IL-1β Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the clinical efficacy of the Qingre Lishi Huazhuo method on patients with chronic gouty arthritis of dampness-heat obstruction syndrome and the effect on nucleotide-binding oligomerization domain-like receptor 3（NLRP3）/interleukin-1β （IL-1β） signaling pathway to preliminarily explore its mechanism. MethodSixty patients with chronic gouty arthritis of dampness-heat obstruction syndrome were enrolled and divided into a treatment group （30 cases） and a control group （30 cases） according to the random number table method. Thirty people were assigned to the healthy group. Patients in the control group were treated with oral Febuxostat， while those in the treatment group were treated with modified Simiaosan combined with Febuxostat. Treatment lasted four weeks. The general clinical data， traditional Chinese medicine （TCM） syndrome scores， serum uric acid （UA）， serum creatinine （SCr）， blood urea nitrogen （BUN）， fasting blood glucose （FPG）， low-density lipoprotein （LDL）， triglyceride （TG）， total cholesterol （TC）， erythrocyte sedimentation rate （ESR）， and C-reactive protein （CRP） of patients were recorded. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of IL-1β，TNF-α， and IL-6，and the levels of NLRP3，cysteinyl aspartate-specific protease-1 （Caspase-1）， and apoptosis-associated speck-like protein containing a CARD （ASC） were detected by Western blot. ResultBefore treatment， the levels of body mass index （BMI）， systolic blood pressure （SBP），diastolic blood pressure （DBP），UA，SCr，BUN，FPG，LDL，TG，and TC in both groups significantly increased （P<0.05，P<0.01），and the levels of HDL significantly decreased as compared with those in the healthy group（P<0.05）. Additionally， the levels of IL-1β， TNF-α， and IL-6 in both groups significantly increased before treatment （P<0.01）. Compared with the results before treatment， patients in the two groups had significant reductions in tube pain， joint tenderness， joint swelling，joint fever， activity disorders， body fatigue， sliminess， bitter mouth， yellow and red urine， and tongue manifestation scores （P<0.05，P<0.01）. Compared with patients in the control group after treatment， those in the treatment group had a significant decrease in joint fever， body fatigue， sliminess， bitter mouth，sticky stool，yellow and red urine， tongue manifestation score， and pulse score （P<0.05）. The total effective rate in the treatment group was 80.0% （24/30）， higher than 56.7% （17/30）in the control group（χ2=11.916，P<0.05）. Compared with the results before treatment， BMI， SBP， DBP， UA， SCr， BUN， FPG， LDL， TG， TC， ESR，CRP， IL-1β， TNF-α， IL-6 levels， and VAS score in both groups significantly decreased （P<0.05，P<0.01）. Compared with patients in the control group after treatment， those in the treatment group had decreased DBP，ESR， IL-1β levels， and VAS score （P<0.05）. Western blot results showed that before treatment， the protein expression of NLRP3， Caspase-1， and ASC in peripheral blood mononuclear cells （PBMCs） of patients in both groups were higher than those in the healthy group （P<0.01）. Compared with the results before treatment， the protein expression of NLRP3， Caspase-1， and ASC in PBMCs in patients of both groups after treatment decreased （P<0.05，P<0.01）. Compared with the control group after treatment， the treatment group showed decreased expression levels of NLRP3 and Caspase-1（P<0.05）. ConclusionThe Qingre Lishi Huazhuo method can effectively improve the clinical symptoms and reduce inflammation of chronic gouty arthritis of dampness-heat obstruction syndrome with good safety. The mechanism may be related to the inhibition of the NLRP3/IL-1β signaling pathway.

The role of CYP1A1/2 in cholesterol ester accumulation provides a new perspective for the treatment of hypercholesterolemia

Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.

RBM46 is essential for gametogenesis and functions in post-transcriptional roles affecting meiotic cohesin subunits

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.