The chemical constituents from the n-butanol fraction of ethanol extract of safflower (Carthamus tinctorius L.) were isolated and purified using chromatographic process including MCI Gel CHP-20, ODS, Sephadex LH-20 column chromatography, and semi-preparative HPLC method, and one alkyne and two phenylpropanoid derivants were obtained. Their structures were identified as (5R,E)-tetradecane-12-ene-8,10-diyne-1,5,14-triol (1), (E)-8-O-β-D-glucopyranosyl n-butyl cinnamate (2), and (7S,8S)-7-(4-hydroxy-3-methoxybenzene)-7-butyl-8,9-diol (3) by modern spectroscopy methods (1D NMR, 2D NMR, UV, IR and MS). 1-3 are all new compounds. Compounds 1-3 were screened for their anti-renal fibrosis activities in vitro, and none of them showed obvious effect.

The purpose of this study was to clarify the effect of Huotan Jiedu Tongluo Decoction on atherosclerosis(AS) injury in ApoE~(-/-) mice by regulating the ferroptosis pathway. Seventy-five ApoE~(-/-) mice were randomly divided into model group, low-, medium-, and high-dose of Huotan Jiedu Tongluo Decoction groups, and evolocumab group(n=15), and 15 C57BL/6J mice were selected as the blank group. Mice in the blank group were fed with a normal diet, and those in the other groups were fed with a high-fat diet to induce AS. From the 9th week, mice in Huotan Jiedu Tongluo Decoction groups were administrated with Huotan Jiedu Tongluo Decoction at corresponding doses by gavage, and those in the blank group and the model group were given an equal volume of distilled water. Mice in the evolocumab group were treated with evolocumab 18.2 mg·kg~(-1 )by subcutaneous injection every 2 weeks. After 8 weeks of continuous intervention, oil red O staining and hematoxylin-eosin(HE) staining were employed to observe the lipid deposition and plaque formation in the aortic root. Masson staining was used to evaluate the collagen content in the aortic root. The serum levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were determined by biochemical kits. The levels of Fe~(2+), superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the aorta were measured by colorimetry. The protein and mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), and acyl-CoA synthetase long chain family member 4(ACSL4) in the aorta were detected by Western blot and RT-qPCR, respectively. The expression of Nrf2, GPX4, and SLC7A11 was localized by immunofluorescence. The results showed that low-, medium-, and high-dose Huotan Jiedu Tongluo Decoction reduced the plaque formation of aortic root and increased the collagen content in AS mice. At the same time, Huotan Jiedu Tongluo Decoction improved the lipid metabolism by lowering the levels of TC, LDL-C, and TG and elevating the level of HDL-C in the serum. Huotan Jiedu Tongluo Decoction enhanced the antioxidant capacity by elevating the levels of GSH and SOD and lowering the level of MDA in the aorta and inhibiting the accumulation of Fe~(2+) in the aorta. In addition, Huotan Jiedu Tongluo Decoction up-regulated the protein and mRNA levels of Nrf2, GPX4, and SLC7A11, while down-regulating the protein and mRNA levels of ACSL4. In summary, Huotan Jiedu Tongluo Decoction can effectively alleviate AS lesions in ApoE~(-/-) mice by activating the Nrf2/GPX4 pathway, reducing lipid peroxidation, and inhibiting ferroptosis.
Animals ; Ferroptosis/drug effects* ; Atherosclerosis/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/genetics* ; Mice ; Mice, Inbred C57BL ; Apolipoproteins E/metabolism* ; Male ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Signal Transduction/drug effects* ; Humans ; Mice, Knockout

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

The purpose of this study was to enrich the genomic information and provide a basis for further development and utilization of Polygonatum kingianum. The fresh rhizome of P. kingianum was used as the experimental material, and the full-length transcriptome was sequenced by PacBio Sequel platform. The final measured polymerase reads were 1 120 485, with a total of 77.73 GB of data. In NR database, 41 864 homologous sequence alignments were aligned to 5 species; 40 506 were annotated in the KOG database and classified into 26 categories based on their functionality; 69 060 GO annotated 32 functional groups divided into 3 categories: cellular components, molecular functions, and biological processes; 45 779 annotations were added to 145 metabolic pathways in the KEGG database. Among them, there are 127 identified transcripts related to polysaccharide synthesis in the glycolysis/gluconeogenesis metabolic pathway, 144 in the starch and sucrose metabolic pathway, 85 in the amino acid sugar and nucleotide sugar metabolic pathway, and 69 in the fructose and mannose metabolic pathway. In addition, 1 781 transcription factors were detected, distributed in 37 transcription factor families; 180 293 SSR loci were detected, among which single base repeats accounted for the most, accounting for 30.48% of all base repeats, and at least five base repeats, accounting for only 0.14% of single base repeats. The results of this study provide important data supporting for enriching the genomic information of P. kingianum and exploring its effective biosynthetic pathway.

Objective To determine the relationship between methylenetetrahydrofolate reductase(MTHFR)C677T,A1298C and multidrug resistance 1(ABCB1)C3435T gene polymorphisms and the adverse reactions of high-dose methotrexate(HD-MTX)in children with acute lymphoblastic leukemia(ALL).Methods Blood samples of ALL children treated with HD-MTX chemotherapy were collected,and the polymorphic polymorphism of MTHFR C677T,A1298C and ABCB1 C3435T genes were detected by sequencing method.The adverse drug reactions after MTX chemotherapy were evaluated according to the common adverse drug reaction grading criteria.The relationship between MTHFR C677T,A1298C and ABCB1 C3435T gene polymorphisms and HD-MTX adverse drug reactions was analyzed.Results The risk of MTHFR A1298C AC+CC type hepatic injury(grade 2)was higher than AA type[odds ratio(OR)2.350,95％confidence interval(CI)=1.038-5.320,P＜0.05],no correlations were found between MTHFR A1298C and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).ABCB1 C3435T CT type hepatic injury(grade 2)was higher than TT type(OR 5.161,95％CI 1.371-19.424,P＜0.05),ABCB1 C3435T CC+CT type hepatic injury(grade 2)was higher than TT type(OR 4.231,95％CI 1.165-15.362,P＜0.05);no correlations were found between ABCB1 C3435T and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).No correlations wre found between MTHFR C677T and HD-MTX adverse drug reactions(all P＞0.05).Conclusion When treating ALL with HD-MTX,adverse drug reactions can be predicted by detecting MTHFR A1298C and ABCB1 C3435T genotypes,so as to implement more scientific individualized medication.

Nanozyme is novel nanoparticle with enzyme-like activity, which can be classified into peroxidase-like nanozyme, catalase-like nanozyme, superoxide dismutase-like nanozyme, oxidase-like nanozyme and hydrolase-like nanozyme according to the type of reaction they catalyze. Since researchers first discovered Fe₃O₄ nanoparticles with peroxidase-like activity in 2007, a variety of nanoparticles have been successively found to have catalytic activity and applied in bioassays, inflammation control, antioxidant damage and tumor therapy, playing a key role in disease diagnosis and treatment. We summarize the use of nanozymes with different classes of enzymatic activity in the diagnosis and treatment of diseases and describe the main factors influencing nanozyme activity. A Mn-based peroxidase-like nanozyme that induces the reduction of glutathione in tumors to produce glutathione disulfide and Mn²⁺, which induces the production of reative oxygen species (ROS) in tumor cells by breaking down H₂O₂ in physiological media through Fenton-like action, thereby inhibiting tumor cell growth. To address the limitation of tumor tissue hypoxia during photodynamic tumor therapy, the effect of photodynamic therapy is significantly enhanced by using hydrogen peroxide nanozymes to catalyze the production of oxygen from H₂O₂. In pathological states, where excess superoxide radicals are produced in the body, superoxide dismutase-like nanozymes are able to selectively regulate intracellular ROS levels, thereby protecting normal cells and slowing down the degradation of cellular function. Based on this principle, an engineered nanosponge has been designed to rapidly scavenge free radicals and deliver oxygen in time to save nerve cells before thrombolysis. Starvation therapy, in which glucose oxidase catalyzes the hydrolysis of glucose to gluconic acid and hydrogen peroxide in cancer cells with the involvement of oxygen, attenuates glycolysis and the production of intermediate metabolites such as nucleotides, lipids and amino acids, was used to synthesize an oxidase-like nanozyme that achieved effective inhibition of tumor growth. Furthermore, by fine-tuning the Lewis acidity of the metal cluster to improve the intrinsic activity of the hydrolase nanozyme and providing a shortened ligand length to increase the density of its active site, a hydrolase-like nanozyme was successfully synthesized that is capable of cleaving phosphate bonds, amide bonds, glycosidic bonds and even biofilms with high efficiency in hydrolyzing the substrate. All these effects depend on the size, morphology, composition, surface modification and environmental media of the nanozyme, which are important aspects to consider in order to improve the catalytic efficiency of the nanozyme and have important implications for the development of nanozyme. Although some progress has been made in the research of nanozymes in disease treatment and diagnosis, there are still some problems, for example, the catalytic rate of nanozymes is still difficult to reach the level of natural enzymes in vivo, and the toxic effects of some heavy metal nanozymes material itself. Therefore, the construction of nanozyme systems with multiple functions, good biocompatibility and high targeting efficiency, and their large-scale application in diagnosis and treatment is still an urgent problem to be solved. (1) To improve the selectivity and specificity of nanozymes. By using antibody coupling, the nanoparticles are able to specifically bind to antigens that are overexpressed in certain cancer cells. It also significantly improves cellular internalization through antigen-mediated endocytosis and enhances the enrichment of nanozymes in target tissues, thereby improving targeting during tumor therapy. Some exogenous stimuli such as laser and ultrasound are used as triggers to control the activation of nanozymes and achieve specific activation of nanozyme. (2) To explore more practical and safer nanozymes and their catalytic mechanisms: biocompatible, clinically proven material molecules can be used for the synthesis of nanoparticles. (3) To solve the problem of its standardization and promote the large-scale clinical application of nanozymes in biomonitoring. Thus, it can go out of the laboratory and face the market to serve human health in more fields, which is one of the future trends of nanozyme development.

The experience of professor YANG Wen-Hui in treating lumbago disease with YANG's Baliao-acupoints moxibustion is introduced in this paper.YANG Wen-Hui believes that the basic pathogenesis of lumbago disease is'cold causes lower back pain',and based on the philosophical idea of'harmony in Shushu(the ways to cultivate health)',he proposes'YANG's Baliao-acupoints moxibustion'for the treatment of lumbago disease.According to the patient's condition,professor YANG used the acupoints of Shangliao(BL31),Ciliao(BL32),Zhongliao(BL33),and selected the moxa cone like jujube core,soybean or wheat grain,and applied moxibustion with the technique of'San Yang Kai Tai'or'Ruo feng Chui Yun',the number of moxibustion is proportional to the age of the patient.YANG's Baliao-acupoints moxibustion in treating lumbago disease exerts highly and remarkable clinical efficacy,and it was widely acclaimed by the patients.

Schimke immuno-osseous dysplasia (SIOD)caused by SMARCAL1 gene mutations is a rare genetic disorder characterized by multi-system involvement, including T-cell dysfunction, skeletal dysplasia, disproportionate short stature, nephrotic syndrome, and kidney failure. This multidisciplinary consultation involved a 9-year-old boy with intrauterine growth retardation, presenting with short stature, T-cell lymphopenia, proteinuria, and degenerative bone and joint disease. Treatment primarily focused on symptomatic and supportive care. Through the multidisciplinary rare disease consultation, holistic support was provided to the patient, offering comprehensive care from various specialtiesx.We also aim to use this case report to enhance clinicians′ under-standing of SIOD and improve the management and treatment of rare diseases.

Objective To investigate the feasibility of translocation of pedicled buccal fat pad in the treatment of the temporomandibular joint ankylosis(TMJA)by measuring the diameter of buccal fat pad and related anatomical structures of the transverse blood vessels,nerves and temporomandibular joint.Methods A total of 40 adult head and neck specimens were randomly divided into group A and group B,with 20 cases in each group.The morphology of the buccal fat pad in group A was observed,and its size and compression diameter through blood vessels and nerves were measured.The anatomical structures of the temporomandibular joint in group B were observed and measured.Results The volume of buccal fat pad in group A was(10.10±1.10)mL on the left side and(9.70±1.50)mL on the right side.The longitudinal axis length of buccal fat pad was(28.18±1.35)mm on the left side and(29.47±1.12)mm on the right side;Transverse axis length of buccal fat pad was(18.56±1.67)mm on the left side and(18.97±1.73)mm on the right side;There are facial artery,facial vein,maxillary artery branch,facial nerve buccal branch and so on through the buccal fat pad.In group B,the sagittal section of the temporomandibular joint disc presented S-type in 15 cases(75.0%),L-type in 3 cases(15.0%),and transitional type in 2 cases(10.0%).Anterior and posterior diameter of the articular disc was(14.42±1.94)mm on the left side and(15.34±1.37)mm on the right side;inside and outside diameter of the articular disc was(20.18±1.77)mm on the left side and(19.57±1.32)mm on the right side.Branches of maxillary artery and superficial temporal artery were respectively distributed within and outside the joint.Conclusion The pedicled buccal fat pad has a constant anatomical position,abundant blood supply,strong tissue repair,anti-infection ability and"buffer pad"function,which can reduce the formation of scar after surgery for TMJA,reduce the postoperative recurrence rate,and contribute to the recovery of joint function after surgery.

Objective:To explore the risk factors of recurrent contralateral hip fracture within 2 years after operation in elderly patients with hip fracture, construct a nomogram prediction model and validate the model.Methods:A total of 601 elderly patients with hip fracture who underwent surgical treatment in Department of Orthopedics in First Hospital of Shanxi Medical University from June 2018 to June 2020 were selected as research objects by the convenient sampling method. They were divided into the modeling set ( n=421) and the verification set ( n=180). According to the incidence of recurrent contralateral hip fracture within 2 years of follow-up, the modeling set was divided into the recurrent fracture group and the normal group, and the clinical data of the two groups were compared. Logistic regression was used to analyze the risk factors for recurrent contralateral hip fracture in elderly patients within 2 years after surgery. R 3.6 software was used to build a risk factor nomogram model for recurrent contralateral hip fracture. Receiver operating characteristic ( ROC) curve and calibration curve were used to evaluate the differentiation and consistency of the model. Results:In 601 elderly patients with hip fracture, the incidence of recurrent contralateral hip fracture within 2 years after surgery was 8.49% (51/601), among which the incidence of modeling set was 8.31% (35/421) and the incidence of verification set was 8.89% (16/180). In the modeling set, the age, female proportion, osteoporosis proportion, combined internal medical disease proportion and malnutrition proportion of patients in the recurrent fracture group were higher than those in the normal group ( P<0.05). Logistic regression analysis showed that gender, age, osteoporosis and combined internal medical diseases were the factors affecting the recurrence of contralateral hip fracture within 2 years after operation in elderly patients with hip fracture ( P<0.05). The equation for constructing a nomogram prediction model was Logit ( P) = -8.521+0.335×age+ 0.116×female +0.341× osteoporosis +0.280 ×combined internal medical diseases. The modeling set predicted the probability of recurrent contralaterial hip fracture according to the nomogram model, and plotted the ROC curve with sensitivity of 0.826, specificity of 0.804, and area under ROC curve ( AUC) of 0.876. The sensitivity of ROC curve of the validation set was 0.788, the specificity was 0.781, and the AUC was 0.830. After internal verification by Bootstrap method, the prediction model of the modeling set and the verification set were well distinguished, and the prediction probability and the actual incidence were well consistent (Hosmer-Lemeshow χ 2=0.462, P=0.674) . Conclusions:Advanced age, female, osteoporosis and combined internal medical diseases are independent risk factors for recurrent contralateral hip fractures in elderly patients with hip fractures within 2 years after surgery. The nomogram model constructed based on this has high predictive efficacy for recurrent hip fractures, which can be used to assess the risk of recurrent fractures and improve the prognosis of patients.