Design, Synthesis, and Biological Evaluation of Novel Purine Derivatives as Herbicide Safeners.

Mesosulfuron-methyl, an inhibitor of acetolactate synthase (ALS), has been extensively used in wheats. However, it can damage wheat (Triticum aestivum) and even lead to crop death. Herbicide safeners selectively shield crops from such damage without compromising weed control. To mitigate the phytotoxicity of mesosulfuron-methyl in crops, several purine derivatives were developed based on active substructure splicing. The synthesized title compounds underwent thorough characterization using infrared spectroscopy, 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. We evaluated chlorophyll and glutathione contents as well as various enzyme activities to evaluate the safer activity of these compounds. Compounds III-3 and III-7 exhibited superior activity compared with the safener mefenpyr-diethyl. Molecular structure analysis, along with predictions of absorption, distribution, metabolism, excretion, and toxicity, indicated that compound III-7 shared pharmacokinetic traits with the commercial safener mefenpyr-diethyl. Molecular docking simulations revealed that compound III-7 competitively bound to the ALS active site with mesosulfuron-methyl, elucidating the protective mechanism of the safeners. Overall, this study highlights purine derivatives as potential candidates for novel safener development.

Realationship between personality impulsivity and aggressivity in adolescents： the effecting path of sibling relationships / 四川精神卫生

BackgroundIn China， the structure shift from just one-child family to both one-child and more-than-one-child families is happening. Exploring how the sibling relationships effect between adolescent personality impulsivity and aggressivity is of great significance for promoting adolescent mental health as well as maintaining social harmony and stability. ObjectiveTo investigate the effecting path of sibling relationships between personality impulsivity and aggressivity in adolescents， so as to provide references for the prevention of violent and aggressive behavior in adolescents. MethodsFrom February to April， 2023， a total of 1 200 students with sibling relationships from 12 primary and secondary schools in a county of Sichuan province were included by random sampling. Barratt Impulsivity Scale （BIS-11）， Chinese Version of Buss & Perry Aggression Questionnaire （AQ-CV）， and Sibling Relationship Questionnaire （SRQ） were used for cross-sectional investigation. Pearson Correlation Analysis was used to analyze the correlation between the scores of these scales. Bootstrap method was used to test the effecting path of sibling relationships between personality impulsivity and aggressivity. ResultsThe total score of BIS-11 was positively correlated with that of AQ-CV as well as the scores of conflict and competition dimensions in SRQ （r=0.485、0.276、0.280，P<0.01）， while negatively correlated with the score of warmth/intimacy dimension in SRQ （r=-0.383， P<0.01）. The total score of AQ-CV was positively correlated with the scores of conflict and competition dimensions in SRQ （r=0.387， 0.340， P<0.01）， while negatively correlated with the score of warmth/intimacy dimension in SRQ （r=-0.304， P<0.01）. Within SRQ， negative correlations could be observed between the score of warmth/intimacy and scores of conflict and competition （r=-0.307， -0.375， P<0.01）， whereas positive correlation could be observed between the score of conflict and that of competition （r=0.267， P<0.01）. The total effect of personality impulsivity level on aggressivity level in adolescent was 0.480 （P<0.01）. Sibling relationships played a mediating role between personality impulsivity and aggressivity in adolescents. Meanwhile， the indirect effect values of warmth/intimacy， conflict and competition were 0.054， 0.075 and 0.062， with the effect values accounting for 11.21%， 15.70% and 12.93%， respectively. ConclusionThe personality impulsivity of adolescents can directly affect their aggressivity， and sibling relationships may act as an important channel connecting personality impulsivity and aggressivity. ［Funded by 2023 Project of the Psychology and Behavioral Science Research Center of the Deyang Federation of Social Sciences （number， XLYXW2023305）］

Current Situation of Health Technology Assessment in Traditional Chinese Medicine Hospitals / 中国实验方剂学杂志

ObjectiveThis study aims to understand the recognition of practitioners in traditional Chinese medicine （TCM） hospitals on hospital-based health technology assessment （HB-HTA）， assessment needs， challenges， and suggestions， so as to provide references for the future work. MethodThe convenient sampling method was adopted to survey the relevant practitioners in TCM hospitals. The questionnaire included 39 questions in 4 dimensions and was distributed through the online platform Weijuanxing. ResultA total of 244 questionnaires were recovered， and the obtained data were analyzed in SPSS. The results showed that 137 practitioners were very familiar with HB-HTA and there was no significant difference in the recognition of practitioners in different occupations （F=0.251； P=0.778）. The practitioners in Hong Kong， Macao， and Taiwan had lower recognition than those in other regions. In terms of the assessment needs， 127 practitioners believed that it was very necessary to carry out HB-HTA in TCM hospitals in the future. Chinese patent medicines/Chinese herbal medicine decoction pieces （5.91） and TCM appropriate technology （5.57） had higher assessment priority scores. The assessment needs were high for the effectiveness （235 practitioners） and safety （224 practitioners） of health technology. The lack of specialized organization and standardized evaluation process system and the shortage of talents were considered to be the major challenges for the future development in this field. ConclusionThe stakeholders carrying out the health technology assessment in TCM hospitals had certain awareness of HB-HTA. Most practitioners believed that it was necessary to carry out HB-HTA in TCM hospitals in the future， while the work might face challenges such as the lack of organizations and system and the shortage of talents， which requires policy support.

Suppression of Metastatic Ovarian Cancer Cells by Bepridil, a Calcium Channel Blocker.

Although surgery followed by platinum-based therapy is effective as a standard treatment in the early stages of ovarian cancer, the majority of cases are diagnosed at advanced stages, leading to poor prognosis. Thus, the identification of novel therapeutic drugs is needed. In this study, we assessed the effectiveness of bepridil-a calcium channel blocker-in ovarian cancer cells using two cell lines: SKOV-3, and SKOV-3-13 (a highly metastatic clone of SKOV-3). Treatment of these cell lines with bepridil significantly reduced cell viability, migration, and invasion. Notably, SKOV-3-13 was more sensitive to bepridil than SKOV-3. The TGF-ß1-induced epithelial-mesenchymal transition (EMT)-like phenotype was reversed by treatment with bepridil in both cell lines. Consistently, expression levels of EMT-related markers, including vimentin, ß-catenin, and Snail, were also substantially decreased by the treatment with bepridil. An in vivo mouse xenograft model was used to confirm these findings. Tumor growth was significantly reduced by bepridil treatment in SKOV-3-13-inoculated mice, and immunohistochemistry showed consistently decreased expression of EMT-related markers. Our findings are the first to report anticancer effects of bepridil in ovarian cancer, and they suggest that bepridil holds significant promise as an effective therapeutic agent for targeting metastatic ovarian cancer.

Preliminary analysis of mRNA and microRNA differential expression profiles in spinal cord regeneration of Gekko japonicus after tail amputation / 解剖学报

Objective To analyze the expression changes of related mRNA and microRNA(miRNA)during spinal cord regeneration after tail amputation of Gekko japonicus, and to explore the biological effects of differentially expressed mRNA and miRNA during spinal cord regeneration. Methods Fifty Gekko japonicus, the tail amputation model of Gekko japonicus was constructed, divided into normal group, 15 days tail amputation group, and 25 days tail amputation group, 5 in each group, repeat the experiment 3 times, 5 spare. Samples of each group were collected, RNA of each group was extracted and high-throughput sequencing. Bioinformatics analysis identifies differentially expressed mRNA and miRNA between groups, Gene Ontology(GO) enrichment analysis of differentially expressed mRNA functional annotations, and construction of miRNA and mRNA gene regulatory networks related to spinal cord regeneration. Results The differential expression of mRNA and miRNA in the normal and newborn spinal cords of Gekko japonicus was analyzed by sequencing. The 15 days and 25 days tail amputation groups identified 538 and 510 differential mRNA expressions and 446, 127 differential miRNA expressions, respectively. GO analysis found that the differentially expressed mRNA aggregated in biological processes related to cell proliferation and neurodevelopment. In the spinal cord regeneration-related miRNA and its target gene regulatory network, 21 mRNA expression was down-regulated in the 15 days tail amputation group, which was regulated negatively by 41 up-regulated miRNAs; 12 mRNA expression was up-regulated and was regulated by 29 down-regulated miRNAs. In the 25 days tail amputation group, 8 mRNA expression was down-regulated and regulated negatively by 10 up-regulated miRNAs; 20 mRNA expression was up-regulated and regulated by 32 down-regulated miRNAs. Conclusion Through the analysis of the differential expression of miRNA and mRNA in the regenerated spinal cord of Gekko japonicus, the expression changes of mRNA and miRNA in spinal cord regeneration were initially revealed, which provided experimental data for elucidating the molecular mechanism of spinal cord regeneration.

Application of clinical value assessment of treatment protocols in guideline development: taking the WFAS Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine as an example / 中国针灸

To enhance the clinical applicability of guidelines and provide more effective guidance for clinical practice, a clinical value assessment was conducted during the development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine, which involved the evaluation of 59 acupuncture and moxibustion treatment protocols from randomized controlled trials (RCTs). This article introduced the methodology, content and results of the clinical value assessment of RCT-based acupuncture and moxibustion treatment protocols, which involved the integration of historical and contemporary medical evidence and expert consensus. It served as a methodological reference for the future development of acupuncture and moxibustion clinical practice guidelines.

Measurement of the Thermic Effect of Food in a Chinese Mixed Diet in Young People / 生物医学与环境科学（英文）

OBJECTIVE@#To determine the thermic effect of food (TEF) in a Chinese mixed diet in young people.@*METHODS@#During the study, the participants were weighed and examined for body composition every morning. The total energy expenditure (TEE) of the participants was measured by the doubly labeled water method for 7 days, and during this period, basal energy expenditure was measured by indirect calorimetry and physical activity energy expenditure was measured by an accelerometer. The value obtained by subtracting basal energy expenditure and physical activity energy expenditure from TEE was used to calculate TEF.@*RESULTS@#Twenty healthy young students (18-30 years; 10 male) participated in the study. The energy intake of the participants was not significantly different from the Chinese Dietary Reference Intake of energy ( P > 0.05). The percentage of energy from protein, fat and carbohydrate were all in the normal range. The intakes of fruits, milk and dietary fiber of the participants were significantly lower than those in the Chinese Dietary Guidelines ( P < 0.05). There was no significant difference in the body weight of the participants during the experiment ( P > 0.05). When adjusted for body weight, there was no significant difference in either TEE or basal energy expenditure between the male and female participants ( P > 0.05). In addition, there was no significant difference in physical activity energy expenditure and TEF between the male and female participants ( P > 0.05). The percentage of TEF in TEE was 8.73%.@*CONCLUSION@#The percentage of TEF in TEE in a Chinese mixed diet in young people was significantly lower than 10% ( P < 0.001). A value of 10% is usually considered to be the TEF in mixed diets as a percentage of TEE.

Developing process and term analysis of WFAS standard: General Requirements for the Risk Control in the Safe Use of Acupuncture / 中国针灸

In order to promote the application of WFAS standard, General Requirements for the Risk Control in the Safe Use of Acupuncture and the safe practice of acupuncture technology worldwide, the paper introduces the developing process and main contents of this standard, explains the developing purpose, scope, ideas, methods and basis, and analyzes the definition of the relevant terms. Through strictly complied with the development procedure of standard, the terms related to acupuncture risk in this standard are defined. The connotations of 5 special terms are clarified, i.e. "acupuncture risks" "adverse events of acupuncture" "adverse reactions of acupuncture" "acupuncture accidents" and "acupuncture negligence". The range, rank, control flow and source of risk, as well as the control measures are determined. The standard extracts the underlying common problems and basic requirement of the safe practice of acupuncture so as to lay a framework for the development of the relevant technical standards of acupuncture.

Quality evaluation of Qilong Zhuang'er oral liquid based on UHPLC-Q-exactive orbitrap MS and chemometrics analysis / 药学学报

An UHPLC-Q-exactive orbitrap MS method for the simultaneous determination of 19 chemical components in Qilong Zhuang'er oral liquid was established and the quality differences between different batches of samples was compared by chemometric analysis to provide a basis for the quality evaluation of the preparation. The contents of allantoin, L-proline, pyroglutamic acid, hordenine, adenosine, L-phenylalanine, guanosine, L-tryptophan, caffeic acid, calycosin-7-glucoside, verbascoside, isoacteoside, ononin, calycosin, 3-hydroxy-9,10-dimethoxyptercarpan, formononetin, atractylenolide III, atractylenolide II and astragaloside A were analyzed by cluster heat map, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using Hiplot platform and MarkerlynxXS software to comprehensively evaluate the quality difference of different batches of Qilong Zhuang'er oral liquid. The 19 chemical compounds showed good linearity in their respective concentration ranges (r ≥ 0.999). The RSD of precision, repeatability and stability (24 h) tests were all less than 1.94%. The average recovery was 97.24%-102.75% (RSD < 2.74%, n = 6). The 10 batches of samples were divided into two categories by cluster heat map and PCA analysis. 3-Hydroxy-9,10-dimethoxyptercarpan, atractylenolide III, calycosin, atractylenolide II, formononetin, allantoin and caffeic acid were identified as differential markers by PLS-DA. The established multi component quantitative method of Qilong Zhuang'er oral liquid combined with chemometric analysis can provide reference for the quality evaluation of the preparation.

Clinical Comprehensive Evaluation of Jinsang Kaiyin Preparation in Treatment of Acute Pharyngitis/Laryngitis / 中国实验方剂学杂志

ObjectiveTo comprehensively evaluate the clinical application value of four types of Jinsang Kaiyin preparation（JSKYs） and the other two Chinese patent medicines（CPMs） in the treatment of acute pharyngitis/laryngitis，so as to provide evidence for their rational clinical use and regulatory decision-making. MethodAccording to the guideline for clinical comprehensive evaluation of CPM，the effectiveness，safety，economy，innovation，suitability and accessibility of four JSKYs and the other two CPM in the treatment of acute pharyngitis/laryngitis were comprehensively evaluated，which were ranked based on the quantitative scoring tool. Result① Effectiveness：Compared with the control group，JSKYs can improve the total effectiveness rate of acute pharyngitis/laryngitis and improve the symptoms. Network meta-analysis showed that the probability of JSKY ranked the first in terms of total effectiveness rate.② Safety：JSKYs did not show acute toxicity and long-term toxicity. The main adverse reactions were skin rash，abdominal pain，diarrhea，nausea and vomiting，etc，which were similar with the other two CPM.③ Economy：For patients with acute laryngitis（wind heat syndrome），compared with drug A，JinsangKaiyin capsule has the comparable cost-effectiveness. For patients with acute pharyngitis（wind heat syndrome），compared with drug B，JinsangKaiyin capsul has low cost and better effectiveness.④ Innovation：Compared with the other two CPM，the indications of JSKYs have their own unique population. JSKYs have six patent approval certifications and has been approved for sale in the Philippines.⑤ Suitability：Compared with the other two CPM，the investigated doctors，pharmacists and patients all believed that the instruction of JSKY was clearer and easier to understand，the use and storage conditions were more convenient，etc.⑥ Accessibility：JSKYs are included in the category B of the National Basic Medical Insurance（2022 edition），which has good cost-effectiveness and affordability for medical insurance and self paid patients. JSKYs do not contain endangered animals and plants. The supply of raw materials can meet the demand of production at present. ConclusionAs for the drug value calculation，JSKY obtained the highest score. Based on all dimensions of evidence，expert consensus on JSKY is class A，which can be directly converted into decision making.

Research progress on effective components，pharmacological mechanisms and clinical use of Polyporus umbellatus in diuresis-promotion and dampness-clearance / 中国药房

Polyporus umbellatus， as a traditional Chinese medicine for promoting diuresis and clearing dampness， mainly contains steroids and polysaccharides. It is usually used to treat diseases of urinary system. In this paper， the research progress of the effective components， pharmacological mechanisms and clinical use of P. umbellatus in diuresis-promotion and dampness- clearance is reviewed. Steroids such as ergosterone， peroxyergosterone， ergosta-7，22-dien-3-one and P. umbellatus polysaccharide PPS1， PPS2， PPS3， GUMP-1-1 and GUMP-1-2 promote diuresis and eliminate dampness through diuresis， renal protection， anti- inflammatory， bacteriostatic and immunomodulatory effects. Traditional Chinese medicine compound preparations such as P. umbellatus powder， P. umbellatus decoction， and Wuling powder have significant effects in treating urinary tract infections， lithiasis， renal edema and lesions， which providing reference for the further development and application of P. umbellatus.

Clinical observation of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis in the early and mid-term stage / 中国药房

OBJECTIVE To investigate clinical efficacy and safety of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis （KOA） in the early and mid-term stage. METHODS Totally 100 KOA patients were randomly divided into control group and trial group， with 50 cases in each group. Control group received Diacerein capsules orally， 50 mg every time， bid. Trial group additionally received Jipei dilong ointment， once a day， on the basis of control group. Both groups had a treatment course of 4 weeks， and were followed up for 3 months after treatment. The clinical efficacy of 2 groups， visual analogue scale （VAS）， Western Ontario and McMaster University osteoarthritis index （WOMAC） score， Lysholm scores before and after treatment， at 3-month follow-up after treatment were all observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin 1β （IL-1β）， IL-6， superoxide dismutase （SOD）， malondialdehyde （MDA）， nitric oxide （NO）， cartilage oligomeric matrix protein （COMP）， matrix metalloproteinase-13 （MMP-13） and C-telopeptide of type Ⅱ collagen （CTX-Ⅱ） were detected in knee joint fluid. The incidence of adverse drug reactions was recorded. RESULTS After 4 weeks of treatment， total effective rate was 96.0% in trial group and 90.0% in control group， without statistical significance between 2 groups （P＞0.05）. At 3- 2019YFC1712500） month follow-up after treatment， total effective rate of trial group was 94.0%， and was higher than 62.0% of control group（P＜0.05）. After 4 weeks of treatment and at 3-month follow-up after treatment， VAS score， WOMAC score，the contents ofTNF-α， IL-1β， IL-6， MDA， NO， COMP， MMP-13 and CTX-Ⅱ in knee joint fluid of two groups were significantly lower than before； Lysholm score and SOD activity of knee joint fluid were significantly higher than before， and the trial group was significantly better than the control group during the same period （P＜0.05）. And there was no statistical significance in the incidence of adverse drug reactions between two groups（P＞0.05）. CONCLUSION For the treatment of KOA in early and mid- term stage， Jipei dilong ointment combined with diacerein relieve pain， improve knee function by inhibiting inflammatory reaction， reducing oxidative stress and inhibiting chondrocyte and matrix degradation， and have low incidence of adverse drug reactions.

Research progress on anti-inflammatory effects of plant-derived cannabinoid type 2 receptor modulators / 中国中药杂志

Excessive and persistent inflammatory responses are a potential pathological condition that can lead to diseases of various systems, including nervous, respiratory, digestive, circulatory, and endocrine systems. Cannabinoid type 2 receptor(CB2R) belongs to the G protein-coupled receptor family and is widely distributed in immune cells, peripheral tissues, and the central nervous system. It plays a role in inflammatory responses under various pathological conditions. The down-regulation of CB2R activity is an important marker of inflammation and and CB2R modulators have been shown to have anti-inflammatory effects. This study explored the relationship between CB2R and inflammatory responses, delved into its regulatory mechanisms in inflammatory diseases, and summarized the research progress on CB2R modulators from plants other than cannabis, including plant extracts and monomeric compounds, in exerting anti-inflammatory effects. The aim is to provide new insights into the prevention and treatment of inflammatory diseases.

Clinical comprehensive evaluation of Jinsang Liyan Pills/Capsules in treatment of chronic pharyngitis / 中国中药杂志

According to the Guidelines for clinical comprehensive evaluation of Chinese patent medicine(2022 version), this study comprehensively compared the clinical value of Jinsang Liyan Pills/Capsules with that of another commonly used Chinese patent medicine(drug A).(1)Effectiveness: Jinsang Liyan Pills/Capsules had antimicrobial, anti-inflammatory, and pain-relieving effects and can improve the total response rate in the treatment of chronic pharyngitis. Moreover, they took effect faster than the control group.(2)Safety: Jinsang Liyan Pills/Capsules did not cause acute toxicity and long-term toxicity, with low incidence of adverse reactions, which were mild and alleviated after drug withdrawal. Therefore, the risk of Jinsang Liyan Pills/Capsules was under control.(3)Economy: Jinsang Liyan Pills/Capsules had lower cost per course of treatment than drug A. The incremental cost-effectiveness ratio(ICER) of Jinsang Liyan Pills combined with Jinsang Qingyin Pills was-39.97 yuan compared with conventional treatment. The ICER of Jinsang Liyan Pills compared with amoxicilin was 0.01 yuan. The results meant that Jinsang Liyan Pills/Capsules had a cost-effectiveness advantage.(4)Innovation: Jinsang Liyan Pills/Capsules had reasonably formula and wide indications, meeting the clinical needs. Moreover, they had been authorized four patents of advanced manufacturing technology.(5)Suitability: the storage and administration of Jinsang Liyan Pills/Capsules were convenient, with clear instruction of medication.(6) Accessibility: Jinsang Liyan Pills/Capsules had sufficient drug reserve, caused low economic burden of patients, and presented environmental bearing capacity. Finally, Jinsang Liyan Pills/Capsules were scored 79.10 points, and drug A 67.93 points. The experts reached the consensus of grade A for Jinsang Liyan Pills/Capsules, which can be directly converted into decision making. The result of this comprehensive evaluation of Jinsang Liyan Pills/Capsules highlight the clinical advantages in the treatment of chronic pharyngitis and lay a foundation for the standardized research on the clinical basic research of the drug in the future.

Clinical comprehensive evaluation of Jinsang Sanjie Pills/Capsules in treatment of vocal nodule/polyp of vocal cord / 中国中药杂志

This study used health technology assessment methods and multi-criteria decision analysis(MCDA) model, according to the guideline for clinical comprehensive evaluation of Chinese patent medicine, we developed this assessment tool. The comprehensive evaluation score of Jinsang Sanjie Pills/Capsules is calculated based on the additive model. This score is calculated by "quantitative evaluation software v1.0 for clinical comprehensive evaluation of Chinese patent medicines" which developed by the project team. The evaluation yielded the following results.(1)Effectiveness: compared with the control group, Jinsang Sanjie Pills/Capsules can improve the total effectiveness rate of vocal nodule/polyp of vocal cord, and improve the symptoms and signs.(2)Safety: Jinsang Sanjie Pills/Capsules did not show acute toxicity and long-term toxicity. The most common adverse reaction was gastrointestinal system damage, all of the adverse reactions were either improved or cured.(3)Economy: from the perspective of the health system, evaluating the single use or combination of Jinsang Sanjie Pills/Capsules with conventional medication in the treatment of vocal nodule/polyp of vocal cord is relatively effective and cost-effective compared to conventional medication, with a stable cost-effectiveness advantage.(4) Innovation: Jinsang Sanjie Pills/Capsules are used for the treatment of slow throat paralysis(vocal nodules, polyp of vocal cord, thickening of vocal mucosa) caused by heat toxin accumulation, Qi stagnation and blood stasis, and the resulting hoarseness. Jinsang Sanjie Pills/Capsules have good innovation and targeted indications.(5) Suitability: the investigated doctors, pharmacists and patients all believed that Jinsang Sanjie Pills/Capsules have good suitability.(6)Accessibility: Jinsang Sanjie Pills/Capsules are included in the category B of the National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance Drug Catalogue(2021 edition), which have good cost-effectiveness and affordability for medical insurance and self-paid patients. Jinsang Sanjie Pills/Capsules do not contain endangered animals and plants. The supply of raw materials can meet the demand of production at present. The comprehensive evaluation score is 76.06 points. Based on all dimensions of evidence, 71.4% experts consensus on Jinsang Sanjie Pills/Capsules is class A, which can be directly converted into decision making. This study comprehensively evaluated the clinical application value of Jinsang Sanjie Pills/Capsules in the treatment of vocal nodule/polyp of vocal cord, so as to provide evidence for their rational clinical use and regulatory decision-making.

Analysis of Intervention of Erxiantang in Ovariectomized Rats by LC-MS Serum Metabolomics / 中国实验方剂学杂志

ObjectiveTo investigate the changes of endogenous metabolites in serum of ovariectomized rats and the effect of Erxiantang on them based on liquid chromatography-mass spectrometry（LC-MS）. MethodTwenty-four healthy female SD rats were randomly divided into sham-operated group， model group and Erxiantang group（7.5 g·kg-1）， with 8 rats in each group. Bilateral ovarian tissues were excised in the model and Erxiantang groups， and small pieces of adipose tissues were excised in the abdominal cavity of the sham-operated group bilaterally， and gastric administration was started 2 weeks after surgery， and equal volumes of distilled water were gavaged in the sham-operated and model groups. After 12 weeks of administration， blood was collected from abdominal aorta， and non-targeted metabonomics was performed on rat serum by LC-MS， and orthogonal partial least squares-discriminant analysis（OPLS-DA） was used to screen differential metabolites. Metabolic pathway analysis was performed based on Kyoto Encyclopedia of Genes and Genomes（KEGG）， and the levels of key enzymes of metabolic pathways were verified by enzyme-linked immunosorbent assay（ELISA）. ResultThe results of metabonomics showed that 82 differential metabolites between the model group and the sham-operated group were glycerophospholipids， fatty acyls， steroids and steroid derivatives， of which the most significant difference was glycerophospholipids. At the same time， Erxiantang could call back 65 out of 82 differential metabolites， of which 11 were statistically significant， mainly phosphatidylcholine（PC） and lysophosphatidylcholine（LysoPC） in glycerophospholipids， followed by corticosterone and 11-deoxycortisol in steroids and steroid derivatives. Metabolic pathway analysis showed that the pathways of glycerophospholipid metabolism and steroid hormone biosynthesis in model group were changed， and were recovered after the administration of Erxiantang. ELISA results showed that compared with the sham-operated group， serum levels of cholinephosphate cytidylytransferase（CCT）， secretory phospholipase A2（sPLA2） and lysophosphatidylcholine acyltransferase（LPCAT）， which were the key metabolic enzymes of glycerophospholipid metabolite PC and LysoPC， were significantly decreased in the model group（P<0.05， P<0.01）， and choline phosphotransferase 1（CPT1） levels decreased but the difference was not statistically significant， compared with the model group， the levels of CCT， sPLA2 and CPT1 were significantly increased in Erxiantang group（P<0.01）. In addition， compared with the sham-operated group， the levels of cholesterol（TC）， triglyceride（TG） and low density lipoprotein cholesterol（LDL-C） were significantly increased in the model group（P<0.01）， the high density lipoprotein cholesterol（HDL-C） level was decreased（P<0.05）， compared with the model group， the levels of TC， TG and LDL-C were significantly decreased and the level of HDL-C was significantly increased in Erxiantang group（P<0.01）. ConclusionEndogenous metabolites and related metabolic pathways in ovariectomized rats were altered， and Erxiantang can reverse some of the different metabolites and related pathways， such as regulating glycerophospholipid metabolism by regulating metabolic enzymes CCT， sPLA2 and CPT1 to increase the levels of PC and LysoPC， and then improve the pathological changes such as lipid metabolism disorder in ovariectomized rats.

Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.

Cloning, expression and activity analysises of chalcone synthase genes in Carthamus tinctorius / 中草药·英文版

OBJECTIVE@#Flavonoids are the bioactive compounds in safflower (Carthamus tinctorius), in which chalcone synthase (CHS) is the first limiting enzyme. However, it is unclear that which chalcone synthase genes (CHSs) are participated in flavonoids biosynthesis in C. tinctorius. In this study, the CHSs in the molecular characterization and enzyme activities were investigated.@*METHODS@#Putative chalcone biosynthase genes were screened by the full-length transcriptome sequences data in C. tinctorius. Chalcone biosynthase genes in C. tinctorius (CtCHSs) were cloned from cDNA of flowers of C. tinctorius. The cloned gene sequences were analyzed by bioinformatics, and their expression patterns were analyzed by real-time PCR (RT-PCR). The protein of CtCHS in the development of flowers was detected by polyclonal antibody Western blot. A recombinant vector of CtCHS was constructed. The CtCHS recombinant protein was induced and purified to detect the enzyme reaction (catalyzing the reaction of p-coumaryl-CoA and malonyl-CoA to produce naringin chalcone). The reaction product was detected by HPLC and LC-MS.@*RESULTS@#Two full-length CtCHS genes were successfully cloned from the flowers of safflower (CtCHS1 and CtCHS3), with gene lengths of 1525 bp and 1358 bp, respectively. RT-PCR analysis showed that both genes were highly expressed in the flowers, but the expression of CtCHS1 was higher than that of CtCHS3 at each developmental stage of the flowers. WB analysis showed that only CtCHS1 protein could be detected at each developmental stage of the flowers. HPLC and LC-MS analyses showed that CtCHS1 could catalyze the conversion of p-coumaryl-CoA and malonyl-CoA substrates to naringin chalcone.@*CONCLUSION@#CtCHS1 is involved in the biosynthesis of naringin chalcone in safflower.

Research Progress on Biological Matrix Reference Materials in Forensic Toxicology / 法医学杂志

Biological matrix reference material is a reference material that combines the target material with the biological matrix. The biological matrix reference material has higher consistency with the authentic specimens in forensic toxicology, and its application has a positive effect on improving the accuracy of test results. This paper reviews the research on the matrix reference materials corresponding to three common biological test materials (blood, urine and hair). In order to provide reference for the development and application of biological matrix reference materials in forensic toxicology, this paper mainly introduces the research progress of preparation technology of biological matrix reference materials and some existing products and their parameters evaluation.

Exploration and example interpretation of real-world herbal prescription classification based on similarity matching algorithm / 中国中药杂志

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.