Polycystic ovary syndrome （PCOS） is a common gynecological endocrine and reproductive disorder，with the main clinical manifestations including ovulation failure，insulin resistance，hyperandrogenism，and obesity. Its occurrence and development are closely related to cellular regulatory mechanisms such as apoptosis，autophagy，oxidative stress，and inflammatory response. Autophagy，as a clearance mechanism that maintains cellular homeostasis，plays a crucial role in maintaining the growth，development，and maturation of oocytes. Exploring the mechanism of autophagy during the occurrence and development of diseases can help develop treatment methods for PCOS by regulating autophagy. Studies have shown that autophagy plays an important role in the pathogenesis of PCOS，and it can affect the occurrence and development of PCOS through multiple pathways，levels，and targets. Traditional Chinese medicine （TCM） regulates autophagy in ovarian granulosa cells or endometrium of patients with PCOS by targeting the expression of autophagy signaling pathways，regulatory factors，and non-coding single-stranded RNA molecules，thereby alleviating inflammation，regulating metabolism disorders，and balancing hormone levels in PCOS. Accordingly，TCM can ameliorate pathological conditions such as insulin resistance，hyperandrogenism，and ovulation failure in PCOS. This article summarizes the TCM formulas and extracts for the treatment of PCOS，as well as the main autophagy pathways and regulatory factors involved，aiming to provide reference and suggestions for the future treatment of PCOS with TCM by regulating autophagy.

Objective To observe changes in genetic material in the peripheral blood of pediatric patients with vascular malformations after interventional procedures. Methods A total of 108 children with vascular malformations who underwent interventional procedures at Shandong University Affiliated Children’s Hospital between February 2021 and January 2024 were selected as the research subjects. Clinical data and peripheral venous blood samples before and after the interventional procedures were collected from the children. Two biological indicators, γ-H2AX and peripheral blood lymphocyte chromosomal aberration (CA), were used to determine the levels of genetic material damage in children with vascular malformations before and after interventional procedures. Results The median age of the children was 7 years and the median body weight was 27 kg. The median dose-area product (DAP) was 24.20 Gy·cm² and the median DAP/kg was 1.04 Gy·cm²/kg. The incidence rates of both γ-H2AX foci and CA in children with vascular malformations significantly increased after the interventional procedures (Z = 5.924, P < 0.001; Z = 8.515, P < 0.001). The incidence of postoperative CA in 7 children were significantly higher than that in others, approaching or exceeding 4%. The incidence rates of postoperative γ-H2AX foci and CA in children with DAP/kg ≥ 1 Gy·cm²/kg were significantly higher than those in children with DAP/kg < 1 Gy·cm²/kg (U = 7.586, P = 0.031; U = 6.835, P = 0.009). No significant differences were observed in the incidence rates of postoperative γ-H2AX foci and CA among subgroups based on age, body weight, or surgical site. A positive correlation was observed between the difference in the incidence rates of γ-H2AX foci before and after the procedure and DAP/kg (R = 0.493, P = 0.027). Conclusion Ionizing radiation exposure during interventional procedures can increase peripheral blood genetic material damage levels in children with vascular malformations, and the damage levels show a correlation with the radiation dose, with some children being abnormally sensitive. Further research is needed to explore the influencing factors for genetic material damage in children with vascular malformations after interventional procedures, which is of great significance for reducing long-term cancer risks and achieving personalized treatment strategies.

To investigate the effects of phosphorus fertilizer on the morphological traits, active ingredients and rhizosphere soil microbial community of Polygala tenuifolia. The phosphorus fertilizer was calculated in terms of P_2O_5. Five treatments were set up: 0(CK), 17(P1), 34(P2), 51(P3), and 68(P4) kg per Mu(1 Mu≈667 m~2). A randomized block design was adopted. Samples of P. tenuifolia and its rhizosphere soil were collected under different superphosphate fertilizer treatments. Illumina high-throughput sequencing was used to analyze the rhizosphere soil microbial community, 9 morphological traits were measured and the content of 11 active ingredients were determined. The results showed that the whole plant weight, shoot fresh weight, root weight, and root peel thickness were the highest under P1 treatment, increasing by 34.41%, 38.80%, 39.21%, and 3.17% respectively compared to CK. Under P2 treatment, the plant height, stem diameter, root thickness, and core thickness were significantly higher than CK. Phosphorus fertilizer had a significant impact on the content of tenuifolin, sibiricose A5, sibiricose A6, arillanin A, 3,6'-disinapoyl sucrose, and polygalaxanthone Ⅲ. Correlation analysis results showed that the relative abundance of Arthrobacter, Bacillus, norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, MND1 and other bacteria, as well as the relative abundance of Neocosmospora, Paraphoma and other fungi were positively correlated with root diameter, wood core diameter, the whole plant weight, root weight, shoot fresh weight of P. tenuifolia. Bacillus, Neocosmospora, Subulicystidium were significantly positively correlated with oligosaccharides such as 3,6'-disinapoyl sucrose, sibiricose A5、sibiricose A6、glomeratose A、arillanin A and tenuifoliside C. Arthrobacter, Humicola, Aspergillus, Paraphoma were positively correlated with tenuifolin and norank＿f＿Vicinamibacteraceae, norank＿o＿Vicinamibacterales, Fusarium were positively correlated with polygalaxanthone Ⅲ. Evidently, appropriate phosphorus application is conducive to the growth and quality improvement of P. tenuifolia, and can increase the abundance of beneficial microorganisms in the soil.
Rhizosphere ; Phosphorus/pharmacology* ; Soil Microbiology ; Polygala/anatomy & histology* ; Fertilizers/analysis* ; Bacteria/metabolism* ; Soil/chemistry* ; Microbiota/drug effects* ; Plant Roots/metabolism*

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

Objective To investigate the mechanism of miR-135a/MYC-mediated resistance to venaclar treatment in myelodysplastic syndromes(MDS)with acute myeloid leukaemia(AML).Methods Eighty-six cases of patients were selected,including 23 healthy donors(control group),47 MDS patients with vinecella resistance(MDS group),and 16 AML patients with vinecella resistance transformed from myelodysplastic syndrome(AML group).The expression levels of miR-135a and MYC in the tissues of the three groups were detected.THP1 cells were divided into miR-NC group(transfected with nonsense sequence)and miR-135a minics group(transfected with miR-135a minics),and the cells were treated with venaclar concentration of 0,0.01,1,and 100 μmol·L-1 for 24 hours,and then detected the cell viability and apoptosis rate in each group.Results The expression of MYC mRNA were 1.00±0.14,0.21±0.04,and 0.25±0.08 in patients of the NC,MDS,and AML groups,respectively;the protein expression of MYC were 1.00±0.15,1.31±0.12 and 1.49±0.16,respectively(P＜0.05).At the cellular level,miR-135a expression were 1.00±0.11,1.31±0.15 and 1.93±0.23 in the BMSCs,MUTZ-1 and THP1 groups;MYC protein expression were 1.00±0.15,1.57±0.22 and 1.97±0.31,the differences were significant(P＜0.05).The methods showed the cell viability of miR-NC group were(100.00±13.26)％,(92.33±10.28)％,(85.41±11.37)％and(28.24±6.02)％at 0,0.01,1,100 μmol·L-1venaclar drug concentration,respectively;cell viability of miR-135a mimics group were(105.12±12.35)％,(82.11±12.07)％,(46.13±8.06)％and(18.20±5.03)％,respectively,there was statistical difference between the two groups only in the 1 μmol·L-1 venaclar drug concentration(P＜0.05).The methods showed that the apoptosis rates in miR-NC group at 0,0.01,1,100 μmol·L-1 venaclar drug concentration were(100.00±11.45)％,(92.48±12.04)％,(108.72±9.63)％and(207.15±21.49)％,the apoptosis rates in miR-135a mimics group were(106.34±16.21)％,(117.26±10.13)％,(269.41±23.59)％and(184.33±19.28)％,respectively;there was statistical difference between the two groups only in 1 μmol·L-1 venaclar drug concentration(P＜0.05).Conclusion The results of this study reveal that miR-135a/MYC mediates the mechanism of resistance to venaclar in the treatment of MDS and AML.

Objective To observe the clinical value of recombinant human erythropoietin injection in the treatment of anemia after chemotherapy in leukemia patients,and to explore the difference of efficacy of different doses.Methods Patients with anemia complicated by leukemia chemotherapy were selected as the study objects and randomly divided into control group,low-dose group and high-dose group.Patients in the control group received conventional treatment(oral ferrous succinate combined with dietary conditioning),and patients in the low-dose group were given 75 U·kg-1 recombinant human erythrophorin treatment on the basis of the control group,subcutaneous injection 3 times a week.High-dose group was treated with 150 U·kg-1 recombinant human erythropoietin on the basis of control group,subcutaneous injection 3 times a week.All three groups were treated for 4 weeks.The clinical efficacy,the anemia-related indexes,the expression of mitogen-activated protein kinase path-related proteins in bone marrow stromal cells,Karnofsky performance status(KPS)score and safety of the three groups were compared.Result Control group,low-dose group and high-dose group were enrolled in 32,33 and 33 cases,respectively,without shedding patients.After treatment,the total effective rate of control group,low-dose group and high-dose group were 62.50％(20 cases/32 cases),78.79％(26 cases/33 cases)and 87.88％(29 cases/33 cases),respectively.There was statistical significance in the total effective rate of control group and high-dose group(P＜0.05).After treatment,the hemoglobin levels of control group,low-dose group and high-dose group were(108.76±6.82),(112.43±7.31)and(116.27±7.72)g·L-1,respectively;red blood cell counts were(3.08±0.42)× 1012,(3.34±0.39)× 1012 and(3.58±0.45)× 1012·L-1,respectively;hematocrit were 0.28±0.05,0.31±0.06 and 0.35±0.07,respectively;the relative expression levels of phosphorylated extracellular regulatory protein kinase 1/2 were 1.12±0.16,1.23±0.17 and 1.35±0.22,respectively;the relative expression levels of phosphorylated stress-activated protein kinase were 0.83±0.13,0.76±0.11 and 0.69±0.09,respectively;the expression levels of p-P38 were 0.92±0.10,0.86±0.09 and 0.80±0.09,respectively;the KPS scores were(69.35±6.43),(72.84±6.62)and(76.35±6.77)points,respectively.The above indexes in the low-dose group and the high-dose group were compared with the control group,respectively,and the above indexes in the high-dose group were compared with the low-dose group,and the differences were statistically significant(all P＜0.05).The adverse drug reactions in the three groups were mainly skin allergy and gastrointestinal reactions.The total incidences of adverse drug reactions in the control group,low-dose group and high-dose group was 12.50％,18.18％and 18.18％,respectively,with no statistical significance(all P＞0.05).Conclusion Recombinant human erythropoietin can significantly correct chemotherapy related anemia in leukemia,and improve health status,and the curative effect of 150 U·kg-1 was better than 75 U·kg-1.

Objective:This study aimed to compare the audiological characteristics between children with unilateral auditory neuropathy (UAN) and single-sided deafness (SSD) to establish a valid basis for the differential diagnosis of children with UAN.Methods:A retrospective analysis was conducted on audiological and imaging evaluations of children with UAN and SSD who were treated at Beijing Children′s Hospital of Capital Medical University between May 2015 and June 2023. There were 17 children with UAN, comprising 10 males and 7 females, with an average age of 4.7 years. Additionally, there were 43 children with SSD, consisting of 27 males and 16 females, with an average age of 6.5 years. Audiological assessments included Auditory brainstem response (ABR), Steady-state auditory evoked potential (ASSR), Behavioural audiometry, Cochlear microphonic potential (CM), Distortino-product otoacoustic emission (DPOAE), and acoustic immittance test. The results of the audiological assessment and imaging phenotypic between the two groups of children were compared and analyzed by applying SPSS 27.0 statistical software.Results:(1) The UAN group (77.8%) had a significantly higher rate of ABR wave III L than the SSD group (20.9%) ( P<0.01). The PA thresholds at 500 Hz and 1 000 Hz of children with SSD were higher than those of children with UAN, while the ASSR thresholds at 500 Hz, 1000 Hz, 2 000 Hz, and 4 000 Hz of children with SSD were significantly higher than those of children with UAN ( P<0.05). (2) The degree of hearing loss in both UAN and SSD children was predominantly complete hearing loss. The percentage of complete hearing loss was significantly higher (χ2=4.353, P=0.037) in the SSD group (93.0%, 40/43) than in the UAN group (63.6%, 7/11). However, the percentage of profound hearing loss was significantly higher in the UAN group (27.3%, 3/11) than in the SSD group (2.3%, 1/43) ( Fisher′s exact test, P=0.023). In terms of hearing curve configuration, the percentage of flat type was significantly higher in the SSD group (76.7%, 33/43) than in the UAN group (36.4%, 4/11). The proportion of the UAN group (27.3%, 3/11) was significantly higher than that in the SSD group (2.3%, 1/43) in ascending type ( P<0.05). There were no statistically significant differences in the hearing curves of the declining type and other types between the two groups ( P>0.05). (3) The proportion of imaging assessment without abnormality was significantly more common in the UAN group (81.8%) than in the SSD group (37.1%) (χ2=6.695, P=0.015). Conclusions:Compared to children with SSD, the occurrence of wave III L on the ABR test was significantly more common in children with UAN. The percentage of ascending hearing curves was significantly higher in children with UAN than in children with SSD. ASSR thresholds were significantly lower in children with UAN. The normal imaging phenotype was significantly more common in children with UAN than in children with SSD.