Bronchial asthma （BA） is a common chronic inflammatory airway disease characterized by airway hyperresponsiveness and reversible airflow limitation. Lung macrophages （LMs）， as important effector cells of the innate immune system， play an important role in recognizing and engulfing pathogens， clearing harmful particles， and regulating immune responses. LMs can be polarized to M1 （pro-inflammatory） or M2 （anti-inflammatory） in different immune environments and participate in promoting or inhibiting inflammatory response， as well as lung parenchyma injury and repair （airway remodeling）， playing a key role in the BA occurrence and development. Regulating the polarization balance of macrophages can not only inhibit the inflammatory response in the airway and reduce airway hyperresponsiveness， but also improve airway remodeling and immune regulation， reduce airway mucus secretion， and alleviate the clinical BA symptoms. Traditional Chinese medicine and its active ingredients， especially polysaccharides and saponins， can regulate the polarization balance of M1/M2 macrophages. Traditional Chinese medicine compounds can balance the secretion of anti-inflammatory and pro-inflammatory factors by staging treatment and targeting the polarization state of M1/M2 macrophages， inhibit inflammatory response in the airway， reduce airway remodeling， and improve the BA symptoms. This paper summarized the research progress on the regulation of M1/M2 macrophage polarization by traditional Chinese medicine and its active ingredients， aiming to provide scientific evidence for the precise targeted therapy of BA.

Bronchial asthma （BA） is a common chronic inflammatory airway disease characterized by airway hyperresponsiveness and reversible airflow limitation. Lung macrophages （LMs）， as important effector cells of the innate immune system， play an important role in recognizing and engulfing pathogens， clearing harmful particles， and regulating immune responses. LMs can be polarized to M1 （pro-inflammatory） or M2 （anti-inflammatory） in different immune environments and participate in promoting or inhibiting inflammatory response， as well as lung parenchyma injury and repair （airway remodeling）， playing a key role in the BA occurrence and development. Regulating the polarization balance of macrophages can not only inhibit the inflammatory response in the airway and reduce airway hyperresponsiveness， but also improve airway remodeling and immune regulation， reduce airway mucus secretion， and alleviate the clinical BA symptoms. Traditional Chinese medicine and its active ingredients， especially polysaccharides and saponins， can regulate the polarization balance of M1/M2 macrophages. Traditional Chinese medicine compounds can balance the secretion of anti-inflammatory and pro-inflammatory factors by staging treatment and targeting the polarization state of M1/M2 macrophages， inhibit inflammatory response in the airway， reduce airway remodeling， and improve the BA symptoms. This paper summarized the research progress on the regulation of M1/M2 macrophage polarization by traditional Chinese medicine and its active ingredients， aiming to provide scientific evidence for the precise targeted therapy of BA.

Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

ObjectiveTo investigate the association between insulin resistance （IR） and cardiovascular metabolic indicators， including blood pressure， blood lipids， and serum uric acid， in a middle-aged population. MethodsBased on the baseline survey of the Hong Sifang cohort of China National Salt Industry Group， a total of 575 participants were included. According to the homeostasis model assessment of insulin resistance， the participants were divided into an IR group （n=116） and a non-IR group （n=459）. Differences between the two groups were compared using the t-test and chi-square test. Multivariate logistic regression analysis was performed to evaluate the associations between IR and abnormalities in metabolic indicators. ResultsA total of 575 participants were included， including 390 men and 185 women， with a mean age of （48.58 ± 5.14） years and a mean body mass index （BMI） of （24.16 ± 2.97） kg/m². Blood pressure， serum uric acid， and blood lipid levels were significantly higher in the IR group than in the non-IR group （P<0.001）. After adjusting for potential confounders including age， sex， and BMI， IR was independently associated with hypertension， dyslipidemia， and hyperuricemia， with odds ratios （OR） and 95% confidence intervals （CI） of 2.57 （1.61-4.09）， 3.81 （2.36-6.17）， and 2.68 （1.53-4.71）， respectively （all P<0.001）. ConclusionInsulin resistance is significantly associated with multiple cardiovascular metabolic risk factors in the middle-aged population. Monitoring IR may contribute to the early prevention and control of cardiovascular diseases.

[Objective] To investigate the infection and characteristics of hepatitis E virus among blood donors in Hangzhou. [Methods] A total of 5 075 blood samples of blood donors from Zhejiang Provincial Blood Center from September to November 2023 were collected, including 5 037 samples with normal ALT and 38 samples with elevated ALT (>50 U/L). Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-HEV IgM, anti-HEV IgG and HEV-Ag. The Fisher test and Chi-square test were used to evaluate the difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among different levels of ALT. The distribution characteristics of HEV screening in blood donors were analyzed. Univariate and multivariate logistic regression were used to analyze the susceptibility factors of anti-HEV IgM and anti-HEV IgG seropositivity, and the anti-HEV IgM-reactive blood donors were followed up by telephone. [Results] The reactivity rates of anti-HEV IgM, anti-HEV IgG and HEV-Ag in 5 075 blood samples were 0.45%, 22.98% and 0%, respectively. There was no difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among different levels of ALT (P>0.05), and the results of univariate and multivariate logistic regression analysis showed that age was a risk factor for anti-HEV IgM and anti-HEV IgG reactivity in blood donors (P<0.05), while no difference in the reactivity rates of anti-HEV IgM and anti-HEV IgG among blood donors was noticed in gender, occupation and education level (P>0.05). [Conclusion] There is a potential risk of transfusion-transmitted HEV (TT-HEV) in Hangzhou, and a cost-effective HEV screening strategy needs to be established to continue regular HEV surveillance in Hangzhou to assess the risk of infection.

[Objective] To investigate the factors influencing the detection of HLA-C expression by flow cytometry. [Methods] A total of 12 hematopoietic stem cell suspension samples from peripheral hematopoietic stem cell volunteer donors were randomly collected after CD34⁺ cell counting detection. The influence of detecting different number of nucleated cell (500 000, 50 000 and 5 000), sequential order of red blood cell lysis and antibody incubation, and the HLA-C antibody with varied remaining time from the expiration date on the detection results of HLA-C expression by flow cytometry were investigated, respectively. The significance of differences between different groups was analyzed through Student t test. [Results] There was no significant difference in the proportion of HLA-C positive cells and mean fluorescence intensity (MFI) among the three groups with different nucleated cell numbers detected (500 000, 50 000 and 5 000) (P>0.05). The sequential order of red blood cell lysis and antibody incubation had no influence on the proportion of HLA-C positive cells (P>0.05), but HLA-C MFI value was significantly lower when antibody incubation was performed after red blood cell lysis than that when antibody incubation was performed before red blood cell lysis (P<0.05). The proportion of HLA-C positive cells and MFI value detected by HLA-C antibody remaining 24 months from the expiration date were significantly higher than those detected by HLA-C antibody remaining only 5 months from the expiration date (P<0.05). [Conclusion] The present study has investigated the factors of influencing HLA-C expression level by flow cytometry, the results have important reference and application value for standardizing the experimental operation of HLA-C expression and improving the accuracy and comparability of detection results.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Orbitrap-MS）， to identify the in vivo and in vitro chemical components of total phenolic acids in Gei Herba（TPAGH）， and to clarify the pharmacological effects and potential mechanisms of the effective part in promoting acute wound healing and inhibiting scar formation. MethodsUPLC-Q-Orbitrap-MS was used to identify the chemical components of TPAGH and ingredients absorbed in vivo after topical administration. A total of 120 ICR mice were randomly divided into the model group， recombinant human epidermal growth factor（rhEGF） group（4 mg·kg^-1）， and low， medium， and high dose groups of TPAGH（3.5， 7， 14 mg·kg^-1）， with 24 mice in each group. A full-thickness skin excision model was constructed， and each administration group was coated with the drug at the wound site， and the model group was treated with an equal volume of normal saline， the treatment was continued for 30 days， during which 8 mice from each group were sacrificed on days 6， 12， and 30. The healing of the wounds in the mice was observed， and histopathological changes in the skin tissues were dynamically observed by hematoxylin-eosin（HE）， Masson， and Sirius red staining， and enzyme-linked immunosorbent assay（ELISA） was used to dynamically measure the contents of interleukin-6（IL-6）， tumor necrosis factor-α（TNF-α）， vascular endothelial growth factor A（VEGFA）， matrix metalloproteinase（MMP）-3 and MMP-9 in skin tissues. Network pharmacology was used to predict the targets related to the promotion of acute wound healing and the inhibition of scar formation by TPAGH， and molecular docking of key components and targets was performed. Gene Ontology（GO） biological process analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were carried out for the related targets， so as to construct a network diagram of herbal material-compound-target-pathway-pharmacological effect-disease for further exploring its potential mechanisms. ResultsA total of 146 compounds were identified in TPAGH， including 28 phenylpropanoids， 31 tannins， 23 triterpenes， 49 flavonoids， and 15 others， and 16 prototype components were found in the serum of mice. Pharmacodynamic results showed that， compared with the model group， the TPAGH groups showed a significant increase in relative wound healing rate and relative scar inhibition rate（P<0.05）， and the number of new capillaries， number of fibroblasts， number of new skin appendages， epidermal regeneration rate， collagen deposition ratio， and Ⅲ/Ⅰ collagen ratio in the tissue were significantly improved（P<0.05， 0.01）， the levels of IL-6， TNF-α， MMP-3 and MMP-9 in the skin tissues were reduced to different degrees， while the level of VEGFA was increased. Network pharmacology analysis screened 10 core targets， including tumor protein 53（TP53）， sarcoma receptor coactivator（SRC）， protein kinase B（Akt）1， signal transducer and activator of transcription 3（STAT3）， epidermal growth factor receptor（EGFR） and so on， participating in 75 signaling pathways such as advanced glycation end-products（AGE）-receptor for AGE（AGE/RAGE） signaling pathway， phosphatidylinositol 3-kinase（PI3K）/Akt signaling pathway， mitogen-activated protein kinase（MAPK） signaling pathway. Molecular docking confirmed that the key components genistein， geraniin， and casuariin had good binding ability to TP53， SRC， Akt1， STAT3 and EGFR. ConclusionThis study comprehensively reflects the chemical composition of TPAGH and the absorbed components after topical administration through UPLC-Q-Orbitrap-MS. TPAGH significantly regulates key indicators of skin healing and tissue reconstruction， thereby clarifying its role in promoting acute wound healing and inhibiting scar formation. By combining in vitro and in vivo component identification with network pharmacology， the study explores how key components may bind to targets such as TP53， Akt1 and EGFR， exerting therapeutic effects through related pathways such as immune inflammation and vascular regeneration.

BACKGROUND:It has been found that abnormal apoptosis of bone tissue cells induced by abnormal iron metabolism plays an important role in the progression of osteoporosis. OBJECTIVE:To investigate the effect of naringin on iron metabolism and cell apoptosis in bone tissue of rats with osteoporosis. METHODS:Fifty 2-month-old female Sprague-Dawley rats were randomly divided into five groups with 10 rats in each group:sham group,osteoporosis group,naringin low-dose group,naringin high-dose group,and naringin high-dose+DKK-1 group.Except for the sham group,rat models of osteoporosis were established by removing bilateral ovarian tissues in the other groups.At 8 weeks after modeling,rats in the naringin low-and high-dose groups were given 100 and 400 mg/kg/d naringenin by gavage,respectively,and rats in the naringenin high dose+DKK-1 group were given 400 mg/kg/d naringin by gavage and subcutaneous injection of 25 mg/kg/d DKK-1,an inhibitor of the Wnt1 signaling pathway,for 7 consecutive days.Relevant indexes were detected after administration. RESULTS AND CONCLUSION:Compared with the osteoporosis group,naringin could enhance the bone mineral density and serum calcium and superoxide dismutase levels in rats(P<0.05),and reduce the serum levels of osteocalcin,malondialdehyde,and phosphorus(P<0.05),while DKK-1 could partially inhibit the interventional effect of naringin(P<0.05).Results from Micro-CT scanning,hematoxylin-eosin and TUNEL staining showed that compared with the osteoporosis group,naringin significantly improved bone microstructure and reduced the rate of cell apoptosis,while DKK-1 partially inhibited the interventional effect of naringin.Immunofluorescence staining results showed that compared with the osteoporosis group,naringin could reduce the oxygen content,anti-tartaric acid phosphatase expression,and elevate the expression of alkaline phosphatase in active tibia tissues(P<0.05),while DKK-1 could partially inhibit the interventional effect of naringin(P<0.05).Results from Prussian blue staining and immunohistochemical staining showed that compared with the osteoporosis group,naringin reduced iron deposition in bone and liver tissues as well as the expression of transferrin receptor 1(P<0.05),and elevated the protein expression of ferroportin 1(P<0.05)in bone tissue,and DKK-1 partially inhibited the intervention of naringin(P<0.05).PCR and western blot assay of tibia specimens showed that compared with the osteoporosis group,naringin decreased the expression of anti-tartrate acid phosphatase,transferrin receptor 1 and Bax(P<0.05),and elevated the expression of alkaline phosphatase,ferroportin 1,Bcl-2,Wnt1 and β-catenin(P<0.05),while DKK-1 partially inhibited the interfering effect of naringin(P<0.05).To conclude,naringin inhibits the progression of osteoporosis by reducing iron deposition and apoptosis rate in bone tissue,which may be related to the activation of the Wnt1 signaling pathway.

OBJECTIVES: To investigate the clinical features and gene mutation characteristics of combined oxidative phosphorylation deficiency type 7 (COXPD7) caused by mutations in the C12orf65 gene, and to enhance the awareness of this disease. METHODS: A child diagnosed with COXPD7 in the Department of Neurology, Children's Hospital Affiliated to Zhengzhou University in 2021 was included, along with 10 patients reported in the literature. All subjects were analyzed for their genotypes and clinical phenotypes. RESULTS: A total of 11 patients with COXPD7 were included, comprising 1 reported in this study and 10 from the literature. Among the 11 patients, 9 had homozygous mutations in the C12orf65 gene, while 2 had compound heterozygous mutations, which were identified as frameshift or nonsense mutations. The age of onset ranged from 1 day to 2 years, and clinical manifestations included optic nerve atrophy and delays in intellectual and motor development. Eight patients exhibited external ophthalmoplegia, and five patients displayed spastic paralysis. Cranial magnetic resonance imaging revealed optic nerve atrophy in all 11 patients, abnormal brainstem signals in 10 patients, and a lactate peak on brainstem magnetic resonance spectroscopy scans in 3 patients. CONCLUSIONS COXPD7 associated with the C12orf65 gene results from homozygous or compound heterozygous mutations, with primary clinical manifestations of optic nerve atrophy and delays in intellectual and motor development. Some patients may also present with spastic paralysis or external ophthalmoplegia. Cranial imaging reveals symmetrical abnormal signals in bilateral basal ganglia and brainstem, and a lactate peak is observed on brainstem magnetic resonance spectroscopy scans.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Mitochondrial Diseases/genetics* ; Mitochondrial Proteins/genetics* ; Mutation ; Oxidative Phosphorylation ; Infant, Newborn

OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent