1.Differential Analysis on Chemical Composition and Pharmacodynamic Effect Between Combined Decoction and Single Decoction of Famous Classical Formula Huaganjian
Yang WANG ; Gaoju ZHANG ; Ling LI ; Liping CHEN ; Li ZHANG ; Xiao LIU ; Yuyu ZHANG ; Yuan CUI ; Minglong LI ; Chaomei FU ; Xin YAN ; Yuxin HE ; Qin DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):199-207
ObjectiveThrough qualitatively and quantitatively analysis of the differences in chemical composition between the combined decoction and single decoction of Huaganjian and comparison of their core efficacy, to explore the rationality of the flexible clinical application of Huaganjian compound preparations and single-flavored dispensing granules. MethodsUltra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was used to qualitatively analyze the combined decoction and single decoction samples of Huaganjian, and meanwhile, the contents of four index components(geniposide, paeoniflorin, hesperidin and paeonol) were quantitatively analyzed by high performance liquid chromatography(HPLC). Nonalcoholic fatty liver disease(NAFLD) rat model induced by high-fat diet was applied to compare the efficacy of combined decoction and single decoction of Huaganjian. A total of 30 male SD rats were randomly divided into the control group, model group, lovastatin group(1.8 mg·kg-1), combined decoction group(1.26 g·kg-1) and single decoction group(1.18 g·kg-1). After successful modeling, lovastatin group, combined decoction group and single decoction group were given corresponding doses of drugs by intragastric administration every day, and the control group and model group were given equal amounts of normal saline by intragastric administration, after 4 weeks of administration, the serum and liver tissues were collected, and the contents of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in serum of rats were detected, and the liver pathological examination was carried out by hematoxylin-eosin(HE) staining and oil red O staining, so as to compare differences of their efficacy. ResultsSeventy chemical components were initially identified and attributed from the lyophilized powder of the combined decoction and single decoction samples of Huaganjian, and there was no obvious difference in composition between the two. Further quantitative analysis showed that the contents of geniposide, paeoniflorin, hesperidin and paeonol in the combined decoction samples were significantly increased when compared with those of the single decoction samples(P<0.01). The pharmacodynamic results showed that compared with the model group, both the combined and single decoction groups of Huaganjian could improve the liver index of NAFLD rats, reduce the serum levels of AST, ALT, TC, TG and LDL-C, increase the serum level of HDL-C, and ameliorate the pathological changes of liver cell steatosis and fat accumulation. However, there was no significant difference in pharmacodynamic effects between the combined decoction group and the single decoction group. ConclusionThere is no significant difference between the combined decoction and single decoction of Huaganjian in terms of chemical composition, but the contents of the four index components show significantly difference. Both of them can significantly improve the fat accumulation and liver function in NAFLD rats. This study provides a reference basis for the rational clinical application and evaluation of famous classical formula compound preparations and single-flavored dispensing granules.
2.Herbal Textual Research on Tribuli Fructus and Astragali Complanati Semen in Famous Classical Formulas
Jiaqin MOU ; Wenjing LI ; Yanzhu MA ; Yue ZHOU ; Wenfeng YAN ; Shijun YANG ; Ling JIN ; Jing SHAO ; Zhijia CUI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):241-251
By systematically combing ancient and modern literature, this paper examined Tribuli Fructus and Astragali Complanati Semen(ACS) used in the famous classical formulas from the aspects of name, origin, production area, harvesting and processing, clinical efficacy, so as to provide a basis for the development of famous classical formulas containing such medicinal materials. The results showed that the names of Tribuli Fructus in the past dynasties were mostly derived from its morphology, and there were nicknames such as Baijili, Cijili and Dujili. The name of ACS in the past dynasties were mostly originated from its production areas, and there were nicknames such as Baijili, Shayuan Jili and Tongjili. Because both of them had the name of Baijili, confusion began to appear in the Song dynasty. In ancient and modern times, the main origin of Tribuli Fructus were Tribulus terrestris, and ancient literature recorded the genuine producing areas of Tribuli Fructus was Dali in Shaanxi and Tianshui in Gansu, but today it is mainly cultivated in Anhui and Shandong. The fruit is the medicinal part, harvested in autumn throughout history. There is no description of the quality of Tribuli Fructus in ancient times, and the plump, firm texture, grayish-white color is the best in modern times. Traditional processing methods for Tribuli Fructus included stir-frying and wine processing, while modern commonly used is purified, fried and salt-processed. The ancient records of Tribuli Fructus were spicy, bitter, and warm in nature, with modern research adding that it is slightly toxic. The main effects of ancient and modern times include treating wind disorders, improving vision, promoting muscle growth, and treating vitiligo. The mainstream base of ACS used throughout history is Astragalus complanatus. Ancient texts indicated ACS primarily originated from Shaanxi province. Today, the finest varieties come from Tongguan and Dali in Shaanxi. The medicinal part is the seed, traditionally harvested in autumn. Modern harvesting occurs in late autumn or early winter, followed by sun-drying. Ancient texts valued seeds with a fragrant aroma as superior, while modern standards prioritize plump, uniform and free of impurities. Traditional processing methods for ACS included frying until blackened and wine-frying, while modern practice commonly employs purification methods. In terms of medicinal properties, the ancient and modern records are sweet and warm in nature. Due to originally classified under Tribuli Fructus, its effects were thus regarded as equivalent to those of Tribuli Fructus, serving as the medicine for treating wind disorders, additional functions included tonifying the kidneys and treating vitiligo. The present record of its efficacy is to tonify the kidney and promote Yang, solidify sperm and reduce urine, nourish the liver and brighten the eye, etc. Based on the textual research results, it is suggested that when developing the famous classical formulas of Tribuli Fructus medicinal materials, we should pay attention to the specific reference object of Baijili, T. terrestris and A. complanatus should be identified and selected, and the processing method should be in accordance with the requirements of the formulas.
3.Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease: Prospective cohort study and genetic analyses
Wenqiang ZHANG ; Li ZHANG ; Chenghan XIAO ; Xueyao WU ; Huijie CUI ; Chao YANG ; Peijing YAN ; Mingshuang TANG ; Yutong WANG ; Lin CHEN ; Yunjie LIU ; Yanqiu ZOU ; Ling ZHANG ; Chunxia YANG ; Yuqin YAO ; Jiayuan LI ; Zhenmi LIU ; Xia JIANG ; Ben ZHANG
Chinese Medical Journal 2024;137(5):577-587
Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.
4.Screw versus Kirschner wire fixation for lateral humeral condyle fractures in children:a meta analysis
Xiang-Yang YU ; Gai-Ge WU ; Hang WANG ; Ling-An HUANG ; Peng-Cui LI ; Xiao-Chun WEI
China Journal of Orthopaedics and Traumatology 2024;37(4):399-405
Objective To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle frac-tures in children.Methods A systematic search was conducted in PubMed,Embase,the Cochrane library,Web of Science,China National Knowledge Internet(CNKI),Wanfang Datebase from in ception to February 2022.Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included.Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality,their excellent and good rate of fracture healing,malunion,delayed union or nonunion,infection,limitation of elbow flexion or extension(>10°)were ex-tracted and analyzed using software Rev Man 5.3.Results A total of 9 retrospective studies involving 647 patients were includ-ed,with 255 patients in the screw fixation group(including screw combined with Kirschner wire)and 392 patients in the Kirschner wire fixation group.Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[OR=0.22,95%CI(0.09,0.56),P=0.001].There were no significant differences between the 2 groups in excellent and good rate of fracture healing,malunion rate(P>0.05).Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[OR=0.18,95%CI(0.05,0.65),P=0.009].Conclusion For lateral humeral condyle fractures,Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation.There were no significant differences in the excellent and good rate of fracture healing,malunion.In terms of postoperative efficacy and safety of internal fixation,orthopaedic surgeons are more like-ly to recommend screws for fixation of lateral humeral condyle fractures in children.
5.Clinical Features and Prognostic of Patients with Primary Central Nervous System Lymphoma
Li-Tian ZHANG ; Cui-Cui LI ; Qi-Qi JIN ; Hao-Yun JIANG ; Ning-Ning YUE ; Peng-Yun ZENG ; Ling-Ling YUE ; Chong-Yang WU
Journal of Experimental Hematology 2024;32(3):723-732
Objective:To explore the clinical features and prognosis of patients with primary central nervous system lymphoma(PCNSL).Methods:A retrospective analysis was performed on the relationship between clinical features,treatment regimen and prognosis in 46 newly diagnosed patients with primary central nervous system lymphoma who were diagnosed and treated in The Second Hospital of Lanzhou University from January 2015 to September 2022.Fisher's exact probability method was used to analyze the differences in clinical data of different subgroups.Kaplan-Meier survival curve was used to analyze the overall survival rate and progression-free survival rate of patients with different treatments,and the factors influencing survival were analyzed.Results:Among 46 patients with PCNSL,which pathological type were diffuse large B-cell lymphoma(DLBCL).There were 26(56.5%)cases of male and 20(43.5%)of female,with a median age of 54(17-71)years.In Hans subtypes,14 cases(30.4%)of GCB subtype,32 cases(69.6%)of non-GCB subtype.32 cases(69.6%)of Ki-67 ≥80%.Among 36 patients who completed at least 2 cycles of treatment with follow-up data,the efficacy evaluation was as follows:overall response rate(ORR)was 63.9%,complete response(CR)rate was 47.2%,17 cases of CR,6 cases of PR.The 1-year progression-free survival rate and 1-year overall survival rate was 73.6%and 84.9%,respectively.The 2-year progression-free survival rate and 2-year overall survival rate was 52.2%and 68.9%,respectively.The ORR and CR rate of 17 patients treated with RMT regimen was 76.5%and 52.9%(9 cases CR and 4 cases PR),respectively.Univariate analysis of 3 groups of patients treated with RMT regimen,RM-BTKi regimen,and RM-TT regimen as first-line treament showed that deep brain infiltration was associated with adverse PFS(P=0.032),and treatment regimen was associated with adverse OS in PCNSL patients(P=0.025).Conclusion:Different treatment modalities were independent prognosis predictors for OS,the deep brain infiltration of PCNSL is a poor predictive factor for PFS.Patients with relapse/refractory(R/R)PCNSL have a longer overall survival time because to the novel medication BTKi.They have strong toleration and therapeutic potential as a first-line therapy for high-risk patients.
6.Prenatal diagnosis of microcephaly due to CTNNB1 frameshift variation: a case report
Haiyu LI ; Weifang TIAN ; Yanhua DONG ; Yangyang WANG ; Handuo WANG ; Jia PENG ; Bo YANG ; Xueyin CUI ; Shihong CUI ; Ling LIU
Chinese Journal of Perinatal Medicine 2024;27(5):417-420
This article reported a case of neurodevelopmental disorder accompanied by spastic diplegia and visual impairment with the manifestation of small fetal head circumference. Prenatal ultrasonography performed at 33 +5 weeks of pregnancy revealed small fetal head circumference (-2.61SD) and oligohydramnios. Whole-exome sequencing identified a heterozygous frameshift variation of c.1623_1624insA (p.R542Tfs*30) in the CTNNB1 gene (NM_001904.4) of the fetus. No phenotypic abnormalities or corresponding gene variations were detected in the parents, suggesting it was a de novo variation. Based on the clinical manifestations, the fetus was diagnosed with a neurodevelopmental disorder accompanied by spastic diplegia and visual defects. Following genetic counseling, the pregnant woman chose to terminate the pregnancy.
7.Common fault maintenance of reverse osmosis water treatment system:3 case reports
Jian-Ming SU ; Yang-Qing GAN ; Shao-Kang CUI ; An LU ; Ling-Jun MENG
Chinese Medical Equipment Journal 2024;45(5):118-120
The basic structure and principle of the reverse osmosis water treatment system were described briefly.Three common faults of the system were explored in terms of cause and solution.References were provided for medical engineers to treat similar faults.[Chinese Medical Equipment Journal,2024,45(5):118-120]
8.Investigation of Effect of Different Processed Products of Atractylodes chinensis Rhizoma on Rats with Spleen Deficiency Based on Pharmacodynamics and Metabolomics
Jiayang LING ; Yang BAI ; Yang QU ; Mingyang CUI ; Xingyi LI ; Qian CAI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):179-188
ObjectiveTo clarify the differences in the efficacy and mechanism of different processed products of Atractylodes chinensis rhizoma by the pharmacodynamics and metabolomics studies of raw, bran-fried and rice water-processed products on rats with spleen deficiency. MethodSixty male SD rats were randomly divided into blank group, model group, raw product group(3.75 g·kg-1), bran-fried product group(3.75 g·kg-1), rice water-processed product group(3.75 g·kg-1) and Shenling Baizhusan group(6.7 g·kg-1), with 10 rats in each group. The method of excessive fatigue+improper diet was used to establish a spleen deficiency model in rats. After the end of modeling, except for the blank and model groups, each dosing group was given the corresponding drug suspension, the immune organ coefficients of each group of rats were examined, the levels of interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), immunoglobulin G(IgG), amylase(AMS), motilin(MTL), gastrin(GAS), Na+-K+-adenosine triphosphatase(ATPase), aquaporin 2(AQP2), AQP3 and AQP8 in rats were measured by enzyme-linked immunosorbent assay(ELISA). Ultra high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) combined with orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to search for biomarkers in the plasma samples of spleen-deficient rats by using two criteria[P<0.05 and variable importance in the projection(VIP) value>1], and to compare the different modulatory effects of the three decoction pieces on the splenic-deficient biomarkers, and metabolic pathway analysis was conducted through the Kyoto Encyclopedia of Genes and Genomes(KEGG) database. ResultCompared with the blank group, the thymus index and spleen index of rats in the model group were significantly decreased(P<0.05), the levels of IL-6, TNF-α, IgG and AQP2 were significantly increased(P<0.05), the levels of AMS, GAS, MTL, AQP3, AQP8 and Na+-K+-ATPase were significantly decreased(P<0.05). Compared with the model group, raw products, bran-fried products and rice water-processed products all increased thymus index and spleen index(P<0.05), decreased IL-6, TNF-α, IgG and AQP2 levels(P<0.05), and increased AMS, GAS, MTL, AQP3, AQP8 and Na+-K+-ATPase levels to different degrees. A total of 176 differential metabolites were screened in the model group compared with the blank group, of which 75, 72 and 84 biomarkers were called back by the raw products, bran-fried products and rice water-processed products, respectively(P<0.05, P<0.01). Raw products of A. chinensis rhizoma mainly affected glycine, serine and threonine metabolism. Bran-fried products mainly affected alanine, aspartate and glutamate metabolism, D-arginine and D-ornithine metabolism. Rice water-processed products mainly affected glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, citrate cycle, thiamine metabolism, D-arginine and D-ornithine metabolism. ConclusionRaw products, bran-fried products and rice water-processed products of A. chinensis rhizoma all have good spleen strengthening effects, among which the effects of bran-fried products and rice water-processed products were stronger. Meanwhile, raw products has the strongest dryness, followed by bran-fried products, and the weakest dryness of rice water-processed products. The three decoction pieces are able to significantly modulate metabolic abnormalities in spleen-deficient rats, and the mechanism may be related to amino acid metabolism such as glycine, serine and threonine metabolism as well as alanine, aspartate and glutamate metabolism.
9.Research status of small ubiquitin-like molecules modification in lung development
The Chinese Journal of Clinical Pharmacology 2024;40(4):624-628
Small ubiquitin-like molecules(SUMO)regulate the function of a variety of cells by binding to target proteins.SUMO modification plays an important role in embryonic development,including heart,brain,liver,etc.Factors involved in lung development and maturation are regulated by SUMO modification,such as hypoxia-inducible factor,CCAAT enhancer-binding protein α,forkhead box protein M1,vascular endothelial-derived growth factor,and bone morphogenetic protein 4,thus affecting their activities and stabilities.Therefore,the SUMO modification status of target protein is the key to explore the development process of fetal lung.In this paper,we reviewed the research literature of SUMO mediated lung development in recent years,and combined with the research basis of our research group for many years,reviewed the factors regulating lung development and the SUMO status,in order to provide ideas for the study of drugs for effective prevention and treatment of pulmonary dysplasia.
10.Synthesis and activity evaluation of 6-azazindole derivatives for pancreatic cancer therapy
Yang CAO ; Qian LI ; Ya-ling WANG ; Wen-hui CUI ; Chen-liang QIAN ; Xin-xin SI
Acta Pharmaceutica Sinica 2024;59(10):2828-2835
Fragment with some anti-pancreatic cancer activity was identified by screening our internal chemical library. Eighteen compounds in 4 classes were synthesized by systematic modification and their anti-pancreatic cancer activity were evaluated. Ⅱ-1 (IC50 = 6.40 ± 0.34 μmol·L-1) and Ⅱ-2 (IC50 = 7.15 ± 0.51 μmol·L-1) exhibited outstanding activity. Subsequently, the anti-migration ability and invasion ability of Ⅱ-1 was evaluated by wound healing assay and invasion assay, Ⅱ-1 exhibited good anti-migration ability and outstanding anti-invasion ability. Using molecular docking technology and molecular dynamics simulation technology, the potential target was locked on bispecific tyrosine phosphorylation regulates kinase 1A (DYRK1A). By enzyme activity testing, the inhibitory capacity of Ⅱ-1 and Ⅱ-2 was 48% and 32%, respectively.

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