OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

The interaction between m⁶A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m⁶A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m⁶A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease characterized by abnormal deposition of lipid in hepatocytes. If not intervened in time, NAFLD may develop into liver fibrosis or liver cancer, and ultimately threatening life. NAFLD has complicated etiology and pathogenesis, and there are no effective therapeutic means and specific drugs. Currently, insulin sensitizers, lipid-lowering agents and hepatoprotective agents are often used for clinical intervention, but these drugs have obvious side effects, and their effectiveness and safety need to be further confirmed. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a central role in maintaining energy homeostasis. Activated AMPK can enhance lipid degradation, alleviate insulin resistance (IR), suppress oxidative stress and inflammatory response, and regulate autophagy, thereby alleviating NAFLD. Natural herbal medicines have received extensive attention recently because of their regulatory effects on AMPK and low side effects. In this article, we reviewed the biologically active natural herbal medicines (such as natural herbal medicine formulas, extracts, polysaccharides, and monomers) that reported in recent years to treat NAFLD via regulating AMPK, which can serve as a foundation for subsequent development of candidate drugs for NAFLD.

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

Objective To evaluate the bioequivalence of the test preparation and reference preparation of azithromycin capsules in healthy Chinese subjects.Methods A total of 48 subjects were enrolled in this study using a randomized,open,two-sequence,cross design.Each subject received a single oral dose of azithromycin capsules test drug(T)or reference drug(R)for 250 mg.The concentrations of azithromycin in plasma were determined by Liquid Chromatograph Mass Spectrometer,and the pharmacokinetic parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.Results The main pharmacokinetic parameters of azithromycin after a single fasting dose of the test drug and the reference drug were as follows:the Cmax were respectively(319.89±127.35)and(330.41±122.11)ng·mL-1;AUC0-192h were respectively(2 423.04±587.15)and(2 489.97±685.73)ng·h·mL-1;AUC0-∞ were respectively(2 753.40±644.96)and(2 851.71±784.05)ng·h·mL-;tmax were respectively(2.60±1.11)and(2.62±1.13)h;t1/2 were respectively(76.76±15.14)and(79.83±17.14)h.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-192h and AUC0-∞ of T and R were 87.52％-107.18％,91.46％-105.80％and 91.17％-105.06％,respectively.Conclusion The test preparation of azithromycin capsule was bioequivalent to the reference preparation under fasting condition.

Lattice strain ruthenium nanoparticles uniformly and stably supported on nitrogen-modified carbon nanosheets(RuNPs/NC)were prepared via simple wet-chemical and subsequent pyrolysis method.The nitrogen doped NC could effectively improve their uniform dispersion and lattice compression of RuNPs.Through changing the pyrolysis temperature,the nitrogen content,types and degree of lattice strain of RuNPs could be effectively tuned,which could be used to adjust and control their peroxidase-like activity.The as-prepared RuNPs/NC-900 exhibited highest peroxidase-like activity,and could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine(TMB)to produce a blue product with the maximum absorption at 652 nm in the presence of H2O2.The steady-state kinetic analysis indicated that the reaction catalyzed by RuNPs/NC followed the Michaelis-Menten kinetic model.Tannic acid(TA),gallic acid(GA)and ascorbic acid(AA)could effectively inhibit the RuNPs/NC-H2O2-triggered chromogenic reaction of TMB,resulting in color fading and decrease in absorbance.Based on this,a sensitive and accurate system was constructed for detection of TA,GA and AA.The detection limits(3σ/S)for TA,GA and AA were 0.014,0.014 and 0.29 μmol/L,respectively.This study not only developed a colorimetric sensing method based on RuNPs/NC nanozyme but also offered a new approach for the sensitive detection of antioxidants in food.

Objective This study aims to investigate the regulatory effects of Fujiu Patch(composed of Sinapis Semen,Kansui Radix,Corydalis Rhizoma and Asari Radix et Rhizoma)on the CD4+ T helper 17 cell(Th17)/CD4+CD25+ regulatory T cell(Treg)balance in asthmatic rats via the signal pathway of IL-6/signal transducer and activator of transcription 3(STAT3)as well as IL-2/signal transducer and activator of transcription 5(STAT5),and to reveal its anti-asthma mechanisms.Methods An experimental asthma model was constructed by ovalbumin(OVA)combined with aluminum hydroxide sensitization and challenge,and then the rats were administered with Fujiu Patch at Dazhui(DU14),Feishu(BL13)and Shenshu(BL23)points for 4 hours each time,once every other day for 7 times.Immunohistochemistry was used to detect the positive expressions of Th17 specific cytokine(IL-17)and Treg transcription factor(Foxp3)in rat lung tissue.The percentage of Th17 and Treg cells in peripheral blood was examined by flow cytometry analysis,and the expressions of IL-6/STAT3 and IL-2/STAT5 pathway-related proteins in lung tissue were assayed with Western Blot.Results Compared to the model group,IL-17 positive expression in the rat lung showed a significant reduction in the Fujiu Patch group(P＜0.01),while the positive expression of Foxp3 was obviously increased(P＜0.05).Meanwhile,the protein expression levels of IL-6 and phospho-STAT3 were were significantly declined(P＜0.01),and the protein expression levels of IL-2 and phospho-STAT5 were were significantly elevated(P＜0.01).However,there was no significant alteration in the total protein expressions of STAT3 and STAT5(P＞0.05).Furthermore,the proportion of Th17 cells in peripheral blood of rats in the Fujiu Patch group was lower than that in the model group,while the proportion of Treg cells was higher than that in the model group.Statistically-significant differences were observed(all P＜0.01).Conclusion These findings indicate that Th17/Treg immune imbalance occurs in asthmatic rat.Fujiu Patch may exert anti-asthma effects via inhibiting the expression of IL-6,downregulating the expression of phospho-STAT3,diminishing the level of IL-17-producing Th17 cells,as well as increasing the expressions of IL-2-mediated STAT5 phosphorylation,raising the level of Foxp3-expressing Treg cells,promoting Th17/Treg balance and suppressing immune responses in rat with asthma.

Objective To investigate the role of calprotectin S100 A8/A9 complex in evaluating the condition of children with severe Mycoplasma pneumoniae pneumonia(SMPP).Methods A prospective study was conducted among 136 children with Mycoplasma pneumoniae pneumonia(MPP)and 30 healthy controls.According to the severity of the condition,the children with MPP were divided into mild subgroup(40 children)and SMPP subgroup(96 children).The levels of S100 A8/A9 complex and related inflammatory factors were compared between the MPP group and the healthy control group,as well as between the two subgroups of MPP.The role of S100 A8/A9 in assessing the severity of MPP was explored.Results The MPP group had a significantly higher level of S100 A8/A9 than the healthy control group,with a significantly greater increase in the SMPP subgroup(P<0.05).The multivariate logistic regression analysis showed that the increases in serum C reactive protein(CRP)and S100A8/A9 were closely associated with SMPP(P<0.05).The receiver operating characteristic(ROC)curve analysis showed that the combined measurement of serum S100 A8/A9 and CRP had an area under the ROC curve of 0.904 in predicting SMPP,which was significantly higher than the AUC of S100 A8/A9 or CRP alone(P<0.05),with a specificity of 0.718 and a sensitivity of 0.952.Conclusions S100 A8/A9 is closely associated with the severity of MPP,and the combination of S100 A8/A9 with CRP is more advantageous for assessing the severity of MPP in children.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.