Two-dimensional nuclear magnetic resonance (2D NMR) is a widely used technique for structural analysis of small molecular compounds. It can obtain information about the hydrogen-hydrogen correlation, hydrogen-carbon single bond correlation, hydrogen-carbon remote correlation, and hydrogen-hydrogen spatial arrangement of compounds. Thus, 2D NMR has an irreplaceable role in the structure elucidation of small molecular products. However, the sample amount of trace components in phytochemical research is very low, and the traditional sampling method (uniform sampling) has problems of poor spectral quality and too long measure time. Increasing the number of scans results in several hours of the acquisition time for a single two-dimensional spectrum, which in turn causes strain on the NMR machine. The non-uniform sampling (NUS) technique can shorten the acquisition time to a large extent and not affect the quality of 2D NMR data, which greatly improves the efficiency of 2D NMR acquisition. In this paper, fuziline, a small molecular compound in the lateral roots of Aconitum carmichaelii was selected as the research object. Its ¹H-¹³C HSQC, ¹H-¹H COSY, HMBC, and NOESY spectra were acquired by US and NUS methods, respectively. By comparing the integral values of NMR signals of three chemical groups in fuziline, it is confirmed that the NUS technique has the advantages of improving the quality of 2D NMR spectra and shortening the acquisition time in structure elucidation of small molecule compounds. In HMBC spectrum, it was further confirmed that NUS technology can improve the quality of the 2D spectra and the signal resolution. This indicates that NUS technology can improve the efficiency and reliability of the structure elucidation of small molecule compounds.

Processing for deodorization is widely used in the production of animal-derived Chinese medicinal materials. In this study, Heracles Neo ultra-fast gas-phase electronic nose combined with chemometrics was employed to analyze the overall odor difference of Cervi Cornu Pantotrichum(focusing on that derived from Cervus nippon Temminck in this study) before and after processing. The results showed that the electronic nose effectively distinguished between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. HS-GC-MS was used to identify and quantify the volatile components in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum, and 35 and 37 volatile components were detected in the medicinal materials and decoction pieces, respectively. The medicinal materials and decoction pieces contained 28 common volatile components contributing to the odor of Cervi Cornu Pantotrichum. The odor activity value(OAV) of each volatile component was calculated based on the olfactory threshold and relative content. The results showed that there were 17 key odor substances such as isovaleraldehyde, 2-methylbutanal, isobutyraldehyde, hexanal, and methanethiol in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. All of them had bad odor and were the main source of the odor of Cervi Cornu Pantotrichum. The results of principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) showed that there were significant differences in volatile components between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. Based on the thresholds of P<0.05 and Variable Importance in Projection(VIP)>1, 21 differential volatile odor components were screened out. Among them, isopentanol, isovaleraldehyde, 2-methylbutanal, n-nonanal, and dimethylamine were the key differential odor compounds between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. The odor compounds and their relative content reduced, and some flavor substances such as esters were produced after processing with wine, which was the main reason for the reduction of the odor after processing of Cervi Cornu Pantotrichum.
Odorants/analysis* ; Electronic Nose ; Gas Chromatography-Mass Spectrometry/methods* ; Animals ; Volatile Organic Compounds/analysis* ; Deer ; Drugs, Chinese Herbal/chemistry*

This article reports the clinical characteristics and treatment processes of three cases of mucormycosis occurring after hematopoietic stem cell transplantation in children, along with a review of relevant literature. All three patients presented with chest pain as the initial symptom, and metagenomic next-generation sequencing (mNGS) confirmed the mucycete infection early in all cases. Two patients recovered after treatment, while one succumbed to disseminated infection. mNGS has facilitated early diagnosis and treatment, reducing mortality rates. Additionally, surgical intervention is an important strategy for improving the prognosis of this condition.
Humans ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Mucormycosis/etiology* ; Male ; High-Throughput Nucleotide Sequencing/methods* ; Child ; Female ; Metagenomics ; Child, Preschool

The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female ; Humans ; Infant ; Disorder of Sex Development, 46,XY/genetics* ; Leydig Cells/pathology* ; Mutation ; Receptors, LH/genetics* ; Testis/abnormalities*

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

Pulmonary fibrosis is a chronic and progressive lung disease that poses a threat to human health. Current treatment options are limited, highlighting the urgent need for more effective therapeutic strategies. Tetrandrine (TET), a bis-benzylisoquinoline alkaloid extracted from Stephania tetrandra, has been known for its anti-inflammatory and anti-fibrotic effects, but its specific mechanisms remain unclear. This study investigated the anti-fibrotic effects of TET in a chronic model of pulmonary fibrosis, aiming to delineate the molecular mechanisms underlying TET-mediated inhibition of fibroblast activation. The results showed that TET significantly alleviated the pathological changes in a murine model of multiple bleomycin-induced pulmonary fibrosis and effectively inhibited TGF-β1-induced fibroblast activation. Mechanistically, TET predominantly inhibited the TGF-β/SMAD signaling pathway and diminished intracellular reactive oxygen species (ROS) levels. Utilizing CRISPR-Cas9 library screening, we identified that angiotensin II type 1 receptor associated protein (AGTRAP) and membrane palmitoylated protein 6 (MPP6) played important roles in TET's suppressive impact of ROS levels, with the knockout of two genes attenuating TET's antifibrotic activity. All animal treatment procedures were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (IMB-20230406D507). This research not only elucidates the pharmacological mechanism of TET but also provides a novel therapeutic avenue for the treatment of pulmonary fibrosis.

Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem cells, characterized by the proliferation of abnormal primordial cells of myeloid origin in bone marrow, blood and other tissues. At present, the standard induction therapy for AML mainly includes “3+7” standard treatment(anthracycline combined with cytarabine), allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and targeted drug therapy. However, AML cells usually express high levels of P-glycoprotein, which mediates the efflux of chemotherapeutic drugs, which makes AML cells resistant to chemotherapy, resulting in many patients who are not sensitive to chemotherapy or relapse after complete remission. And some patients can not tolerate intensive therapy or lack of donors and can not use Allo-HSCT therapy. Therefore, it is of great clinical significance to find new drugs to improve the efficacy of AML patients. Epigenetic disorders play a key role in the pathogenesis of many diseases, especially cancer. Studies have shown that most AML patients have epigenetic regulatory gene mutations, such as DNMT3A, IDH and TET2, and these mutations are potentially reversible, which has become one of the therapeutic targets of AML. Histone deacetylase inhibitors (HDACi) can regulate the balance between histone acetylation and deacetylation, change the expression of proto-oncogenes or tumor suppressor genes that control cancer progression from epigenetics, and play an important role in many kinds of tumor therapy. At present, HDACi has shown the ability to induce differentiation, cell cycle arrest and apoptosis of AML cells. The mechanism may be mainly related to HDACi inducing chromatin conformation opening of tumor suppressor gene by inhibiting HDAC activity, promoting oncogene damage and preventing oncogene fusion protein from recruiting HDAC. Although the preclinical outcome of HDACi is promising, it is not as effective as the conventional therapy of AML. However, the combination strategy with various anticancer drugs is in clinical trials, showing significant anti-AML activity, improving efficacy through key targeting pathways in a typical synergistic or additive way, increasing AML sensitivity to chemotherapy, reducing tumor growth and metastasis potential, inhibiting cell mitotic activity, inducing cell apoptosis, regulating bone marrow microenvironment, which provides a good choice for the treatment of AML. Especially for those AML patients who are not suitable for intensive therapy and drug resistance to chemotherapy. This review introduces the relationship between HDAC and cancer; the classification of HDAC and its function in AML; the correlation between HDAC and AML; the clinical application of five types of HDACi; preclinical research results and clinical application progress of six kinds of HDACi in AML, such as Vrinota, Belinostat, Panobinostat, Valproic acid, Entinostat, and Chidamide, the mechanism of HDACi combined with other anticancer drugs in AML indicates that the current HDACi is mainly aimed at various subtypes of pan-HDAC inhibitors, with obvious side effects, such as fatigue, thrombocytopenia, nausea, vomiting, diarrhea. In recent years, the next generation of HDACi is mainly focused on the selectivity of analogues or isomers. Finding the best combination of HDACi and other drugs and the best timing of administration to balance the efficacy and adverse reactions is a major challenge in the treatment of AML, and the continued development of selective HDACi with less side effects and more accurate location is the key point for the development of this drug in the future. It is expected to provide reference for clinical treatment of AML.

Objective To investigate the role of bone marrow mesenchymal stem cells derived from diabetic mice and their paracrine roles in inducing insulin resistance(IR).Methods The mouse model of diabetes mellitus was established,bone marrow mesenchymal stem cells(BMSC)were extracted and cultured,and the culture supernatant(M-BMSC-CS)was collected.(1)Cell experiment:HepG2 hepatocytes were divided into normal low-glycemic culture group[cultured with low-glycemic DMEM(5.55 mmol·L-1)],M-BMSC-CS experimental group(M-BMSC-CS 75 μL),and high-glycemic and high-lipid control group(given 25 mmol·L-1 high-glycemic DMEM+0.25 mmol·L-1 palmitic acid);(2)Animal experiments:Mice were divided into normal mice group(0.9％NaCl by intraperitoneal injection)and M-BMSC-CS-m group(M-BMSC-CS by intraperitoneal injection of normal mice(injection dose 0.2 mL/10 g)].Glucose intake was measured by glucose oxidase method.The fluorescence intensity of Glut2 protein was detected by immunofluorescence.The expression of insulin signaling pathway protein was detected by Western blot.Test oral glucose tolerance(OGTT)and insulin tolerance(ITT).Results The glucose intakes of the normal low-glucose culture group,the M-BMSC-CS experimental group and the high-glucose and high-lipid control group were(2.96±0.05),(1.64±0.28)and(1.42±0.32)mmol·L-1,respectively;the fluorescence expressions of glucose transporter 2(Glut2)were 53.21±2.70,30.95±3.39 and 34.96±7.60,respectively;the protein expression levels of phosphorylated insulin receptor substrate 1-ser307(p-IRS-1ser307)were 0.46±0.21,1.09±0.24 and 0.91±0.16,respectively;phosphorylated protein kinase(p-AKT)protein expression levels were 0.94±0.05,0.59±0.06 and 0.53±0.05;Glut2 protein expression levels were 1.08±0.14,0.58±0.14 and 0.62±0.09,respectively.The above indexes in M-BMSC-CS experimental group were statistically significant compared with those in normal low-glycemic culture group(all P＜0.05).Fasting blood glucose levels in the normal group and M-BMSC-CS-m group were(5.23±0.57)and(9.30±1.14)mmol·L-1;p-AKT protein expression level were 1.27±0.21 and 0.51±0.19;Glut2 protein expression level were 1.17±0.17 and 0.79±0.09,respectively.The above indexes in M-BMSC-CS-m group were significantly different from those in normal mouse group(P＜0.05).Conclusion BMSC culture supernatant from diabetic mice induced insulin resistance of normal HepG2 hepatocytes in vitro and normal mice in vivo.

Objective:To evaluate early residual myocardial ischemia after successful percutaneous coronary intervention (PCI) in patients with coronary artery disease by using myocardial perfusion imaging (MPI) and investigate independent influencing factors of early residual myocardial ischemia.Methods:From January 2020 to December 2022, 127 patients (107 males, 20 females; age (60.3±9.6) years) with coronary artery disease who underwent PCI complete revascularization at the First People′s Hospital of Changzhou were consecutively enrolled prospectively. All patients underwent rest and stress MPI within 1-3 months after PCI. Reversible myocardial perfusion defect in the blood supply area of the culprit vessels in stress and rest MPI was defined as early residual myocardial ischemia after PCI. Accordingly, the culprit vessels undergoing PCI were divided into residual ischemic group and non-ischemic group. Differences of cardiovascular examination between two groups were compared ( χ2 test), such as proportion of culprit vessels with severe stenosis (≥90%), proportion of bifurcation lesions, and proportion of diffuse coronary disease. Logistic regression analyses were performed to identify influencing factors for early residual myocardial ischemia. Results:Among 148 culprit vessels undergoing PCI in 127 patients, early residual myocardial ischemia was present in 49 vessels (33.1%, 49/148). The proportion of culprit vessels with severe stenosis before PCI in residual ischemia group was higher than that in non-ischemia group (69.4%(34/49) and 49.5%(49/99); χ2=5.27, P=0.022). The proportion of bifurcation lesions in residual ischemic group was also higher than that in non-ischemic group (28.6%(14/49) and 10.1%(10/99); χ2=8.23, P=0.004), with a slightly higher proportion of diffuse coronary disease compared to non-ischemic group (14.3%(7/49) and 4.0%(4/99); χ2=3.62, P=0.057). Multivariate logistic regression analysis showed that bifurcation lesion (odds ratio ( OR)=4.087, 95% CI: 1.615-10.344, P=0.003) and diffuse coronary disease ( OR=4.208, 95% CI: 1.115-15.878, P=0.034) were independent influencing factors for early residual myocardial ischemia. Conclusions:Early residual myocardial ischemia is still present in about 1/3 of the culprit vessels after PCI complete revascularization. Bifurcation lesion and diffuse coronary disease are independent influencing factors for early residual myocardial ischemia in culprit vessels.

Objective:To evaluate the effect of low-dose recombinant interleukin-2(rIL-2)therapy on immunocyte subsets and its side effects in children with solid tumor.Methods:A total of 22 children(11 males and 11 females)with solid tumor in our department from December 2012 to November 2017 were selected,with a median age of 9(3-16)years old when starting IL-2 therapy.ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy,and 17 cases achieved complete remission(CR)and 5 cases achieved partial remission(PR).A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year:4 × 105 IU/(m2·d),s.c.for every other day,3 times per week.The immunocyte subsets were detected every 3 months until the end of treatment,meanwhile,disease condition and therapy-related side effects were followed up.Results:After low-dose rIL-2 therapy in 22 children,the absolute values of CD3+T cells,CD3-CD56+natural killer cells,CD3+CD4+helper T cells(Th)and CD3+CD8+cytotoxic T cells were up-regulated remarkably,as well as Th/suppressor T cells(all P＜0.05).While,there were no significant differences in absolute value and proportion of CD4+CD25+CD127-Treg cells during therapy.Among the 17 children who achieved CR before rIL-2 therapy,14 cases continued to maintain CR after therapy,while 3 cases relapsed,and with 2 died after treatment abandonment.The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment.In the early stage of low-dose rIL-2 therapy,1 child developed skin rashes at the injection sites,and 2 children ran a slight to mild transient fever.Their symptoms disappeared without any organ damage after symptomatic treatment.Conclusion:Low-dose rIL-2 therapy has good drug tolerance,and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.