BACKGROUND: Quantitative flow ratio (QFR) holds significant value in guiding drug-coated balloon (DCB) treatment and enhancing outcomes. However, the predictive capability of post-angioplasty QFR for long-term clinical events in patients with de novo lesions who receive DCB treatment remains uncertain. The aim of this study was to explore the potential significance of post-angioplasty QFR measurements in predicting clinical outcomes in patients underwent DCB treatment for de novo lesions. METHODS: Patients who underwent DCB-only intervention for de novo lesions were enrolled. QFR was conducted after DCB treatment. The patients were then categorized based on post-angioplasty QFR. The primary endpoint was major adverse cardiac events (MACE), encompassing all-cause death, cardiovascular death, nonfatal myocardial infarction, stroke, and target vessel revascularization. RESULTS: A total of 553 patients with 561 lesions were included. The median follow-up period was 505 days, during which 66 (11.8%) MACEs occurred. Based on post-procedural QFR grouping, there were 259 cases in the high QFR group (QFR > 0.93) and 302 cases in the low QFR group (QFR ≤ 0.93). Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MACE in the low QFR group (log-rank P = 0.004). The multivariate Cox proportional hazards model demonstrated a significant inverse correlation between QFR and the occurrence of MACEs (HR = 0.522, 95%CI: 0.289-0.942, P = 0.031). Landmark analysis indicated that high QFR had a significant reducing effect on the cumulative incidence of MACEs within 1 year (log-rank P = 0.016) and 1-5 years (log-rank P = 0.026). CONCLUSIONS In patients who underwent DCB-only treatment for de novo lesions, higher post-procedural QFR values (> 0.93) were identified as an independent protective factor against adverse prognosis.

OBJECTIVE: To identify the underlying molecular mechanism of Modified Hu-Lu-Ba-Wan (MHW) in alleviating renal lesions in mice with diabetic kidney disease (DKD). METHODS: The db/db mice were divided into model group and MHW group according to a random number table, while db/m mice were settled as the control group (n=8 per group). The control and model groups were gavaged daily with distilled water [10 mL/(kg·d)], and the MHW group was treated with MHW [17.8 g/(kg·d)] for 6 weeks. After MHW administration for 6 weeks, indicators associated with glucolipid metabolism and urinary albumin were tested. Podocytes were observed by transmission electron microscopy. Kidney transcriptomics was performed after confirming therapeutic effects of MHW on DKD mice. The relevant target of MHW' effect in DKD was further determined by enzyme-linked immunosorbent assay, Western blot analysis, immunohistochemistry, and immunofluorescence staining. RESULTS: Compared with the model group, MHW improved glucose and lipid metabolism (P<0.05), and reduced lipid deposition in the kidney. Meanwhile, MHW reduced the excretion of urinary albumin (P<0.05) and ameliorated renal damage. Transcriptomic analysis revealed that the inflammation response, particularly the interleukin-17 (IL-17) signaling pathway, may be responsible for the effect of MHW on DKD. Furtherly, our results found that MHW inhibited IL-17A and alleviated early fibrosis in the diabetic kidney. CONCLUSION MHW ameliorated renal damage in DKD via inhibiting IL-17A, suggesting a potential strategy for DKD therapy.
Animals ; Diabetic Nephropathies/genetics* ; Interleukin-17/antagonists & inhibitors* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Kidney/ultrastructure* ; Podocytes/metabolism* ; Mice ; Albuminuria ; Lipid Metabolism/drug effects* ; Mice, Inbred C57BL

OBJECTIVES: To investigate the role and mechanism of Brahma-related gene 1 (Brg1) in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia (BPD) model. METHODS: Wild-type C57BL/6 and Brg1^f1/f1 mice were randomly divided into four groups: wild-type control, wild-type BPD, Brg1^f1/f1 control, and Brg1^f1/f1 BPD (n=5 each). Immortalized mouse pulmonary alveolar type 2 cells (imPAC2) were cultured, and Brg1 gene was knocked down using lentivirus transfection technology. Cells were divided into three groups: control, empty vector, and Brg1 knockdown. Hematoxylin and eosin staining and immunofluorescence were used to detect pathological changes in mouse lung tissue. Western blot and real-time fluorescent quantitative PCR were used to measure Brg1 protein and mRNA expression levels in mouse lung tissue. Western blot and immunofluorescence were used to detect the expression of homeodomain-containing protein homeobox (HOPX), surfactant protein C (SPC), and Wnt/β-catenin signaling pathway proteins in mouse lung tissue and imPAC2 cells. The CCK8 assay was used to assess the proliferation of imPAC2 cells, and co-immunoprecipitation was performed to verify the interaction between Brg1 and β-catenin proteins in imPAC2 cells. RESULTS: Compared to the Brg1^f1/f1 control group and wild-type BPD group, the Brg1^f1/f1 BPD group showed increased alveolar diameter and SPC protein expression, and decreased relative density of pulmonary vasculature and HOPX protein expression (P<0.05). Compared to the control group, the Brg1 knockdown group showed increased cell proliferation ability, protein expression levels of SPC, Wnt5a and β-catenin, and β-catenin protein fluorescence intensity, along with decreased HOPX protein expression (P<0.05). An interaction between Brg1 and β-catenin proteins was confirmed. CONCLUSIONS The Brg1 gene may promote the proliferation of alveolar type 2 epithelial cells by regulating the Wnt/β-catenin signaling pathway, thus influencing the occurrence and development of BPD.
Animals ; DNA Helicases/genetics* ; Transcription Factors/genetics* ; Wnt Signaling Pathway/physiology* ; Nuclear Proteins/genetics* ; Mice ; Bronchopulmonary Dysplasia/etiology* ; Mice, Inbred C57BL ; beta Catenin/physiology* ; Disease Models, Animal ; Cell Proliferation ; Lung/pathology* ; Male

Kinesiophobia is prevalent among school-aged children with asthma,and severe kinesiophobia can hinder their participation in physical activities and disease control,adversely affecting their physical and mental health.This paper reviews the concept,development,assessment tools,influencing factors,and intervention strategies of kinesiophobia in school-aged children with asthma,analyzes existing challenges,and proposes directions for future research.It aims to provide insights for developing scientific and personalized intervention plans to enhance children's exercise levels and improve their quality of life.

AIM To study the chemical constituents from the sticks and leaves of Croton cascarilloides Raeusch.and their biological activities.METHODS The 95％ethanol extract from the sticks and leaves of C.cascarilloides was isolated and purified by MCI,silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.LPS-induced NO RAW264.7 cell model induced by LPS was used to evaluate its anti-inflammatory activity in vitro.GES-1 injury model induced by taurocholic acid was used to screen the gastric mucosal protection activity.RESULTS Fourteen compounds were isolated and identified as bullatantriol(1),(-)-boscialin(2),(+)-dehydrovomifoliol(3),3-(hydroxylacetyl)-indole(4),pinoresinol(5),3,7-dimethyl-octa-1,7-diene-3,6-ol(6),(+)-syringaresinol(7),curcasinlignan B(8),cleomiscosin C(9),cleomiscosinD(10),2,6-dimethyl-octa-1,7-dien-3,6-diol(11),vanillin(12),vanillic acid(13),methyl vanillate(14).Compound 4 had certain anti-inflammatory activity,with IC50 values of 73.62 μmol/L.The protective rates of 25 μmol/L compounds 1-4,6,9-12 and 14 on gastric mucosal epithelial cells were 30.07％,34.18％,23.91％,30.92％,17.51％,19.69％,31.76％,22.46％,30.56％and 14.49％,respectively.CONCLUSION Compounds 1-14 are isolated from this plant for the first time.Compound 4 shows anti-inflammatory activity,1-4,6,9-12 and 14 show different degrees of gastric mucosal epithelial cell protective activity.

The phase changes and quantity-quality transfer of 17 batches of Ostreae Concha(Ostrea rivularis) during the raw material-calcined decoction pieces-standard decoction process were analyzed. The content of calcium carbonate(CaCO_3), the main component, was determined by chemical titration, and the extract yield and transfer rate were calculated. The CaCO_3 content in the raw material, calcined decoction pieces, and standard decoction was 94.39%-98.80%, 95.03%-99.22%, and 84.58%-90.47%, respectively. The process of raw material to calcined decoction pieces showed the yield range of 96.85% to 98.55% and the CaCO_3 transfer rate range of 96.92% to 99.27%. The process of calcined decoction pieces to standard decoction showed the extract yield range of 2.86% to 5.48% and the CaCO_3 transfer rate range of 2.59% to 5.13%. The results of X-ray fluorescence(XRF) assay showed that the raw material, calcined decoction pieces, and standard decoction mainly contained Ca, Na, Mg, Si, Br, Cl, Al, Fe, Cr, Mn, and K. The chemometric results showed an increase in the relative content of Cr, Fe, and Si from raw material to calcined decoction pieces and an increase in the relative content of Mg, Al, Br, K, Cl, and Na from calcined decoction pieces to standard decoction. X-ray diffraction(XRD) was employed to establish XRD characteristic patterns of the raw material, calcined decoction pieces, and standard decoction. The XRD results showed that the main phase of all three was calcite, and no transformation of crystalline form or generation of new phase was observed. Fourier transform infrared spectroscopy(FTIR) was employed to establish the FTIR characteristic spectra of the raw material, calcined decoction pieces, and standard decoction. The FTIR results showed that the raw material had internal vibrations of O-H, C-H, C=O, C-O, and CO■ groups. Due to the loss of organic matter components after calcination, no information about the vibrations of C-H, C=O, and C-O groups was observed in the spectra of calcined decoction pieces and standard decoction. In summary, this study elucidated the quantity-quality transfer and phase changes in the raw material-calcined decoction pieces-standard decoction process by determining the CaCO_3 content, calculating the extract yield and transfer rate, and comparing the element changes, FTIR characteristic spectra, and XRD characteristic pattern. The results were reasonable and reliable, laying a foundation for the subsequent process research and quality control of the formula granules of calcined Ostreae Concha(O. rivularis Gould), and providing ideas and methods for the quality control of the whole process of raw material-decoction pieces-standard decoction-formula granules of Ostreae Concha and other testacean traditional Chinese medicine.
Drugs, Chinese Herbal/isolation & purification* ; Calcium Carbonate/analysis* ; Quality Control

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the regulatory effect of electroacupuncture on visual cortex plasticity in adult amblyopic mice and its mechanism.Methods:Forty-eight SPF male healthy 3-week-old Kunming mice were randomly divided into a normal control group, a monocular form deprivation (MD) group, and an electroacupuncture intervention group by the random number table method, with 16 mice in each group.Except for the normal control group, mice in the other groups had their right eyelids sutured for two weeks to establish an adult MD amblyopia model.The electroacupuncture intervention group received electroacupuncture stimulation at three acupoints, Taiyang (EX-HN5), Jingming (BL1), and Fengchi (GB20) for four weeks at five weeks of age.The subjective visual function (paw probing success rate) of each group of mice was measured at five and nine weeks of age, respectively.At nine weeks of age, the changes in flash-visual evoked potential (F-VEP) of mice in each group was detected.The expression of plasticity related proteins synaptophysin (SYP), synaptic protein 1 (SYN1), neurite overgrowth inhibitor A (Nogo-A), and Nogo receptor (NgR) proteins in the contralateral cortex of the deprived mouse eyes was detected by Western blot.Expression of early growth response gene 1 (Egr-1) in the visual cortex of mice was detected by immunohistochemical staining.This study was approved by the Animal Ethics Committee of Hunan Children's Hospital (No.HCHDWLL-2022-17), and the management and use of animals were in accordance with the Laboratory Animal Management and Use Guide of Hunan Children's Hospital.Results:At nine weeks of age, the success rates of paw probing in the normal control group, MD group, and electroacupuncture intervention group were (71.69±10.60)%, (25.54±10.09)%, and (58.25±8.39)%, respectively, with a statistically significant overall difference ( F=5.987, P=0.006).Among them, the success rate of paw probing was significantly lower in the MD group than in the normal control group, and the electroacupuncture intervention group was significantly higher than in the MD group (both P<0.05).There was a significant overall difference in P2 wave amplitude in F-VEP examination among different groups of mice ( F=63.710, P<0.001), with lower P2 wave amplitude in the deprived eye of the MD group than in the normal control group and the electroacupuncture intervention group, and the differences were statistically significant (both P<0.001).There were significant differences in the expression levels of SYP and SYN1 proteins in the contralateral cortex of the deprived mouse eyes ( F=5.451, 3.871; both P<0.05).The relative expression levels of SYP and SYN1 proteins were significantly lower in the MD group than in the normal control group and electroacupuncture intervention group (all P<0.05).There were significant differences in levels of Nogo-A and NgR proteins in the contralateral cortex of the deprived mouse eyes ( F=4.188, 3.942, both P<0.05).The relative expression levels of Nogo-A and NgR proteins were significantly higher in the MD group than in the normal control group and the electroacupuncture intervention group (all P<0.05).The immunohistochemical staining results showed that compared with the normal control group, the MD group mice had a decrease in the expression of Egr-1 in the contralateral cortical neurons of the deprived eye, and the brown neuron protrusions were indistinguishable.Compared with the MD group, the electroacupuncture intervention group showed significant positive cell expression in the contralateral cortical area of the deprived eye, but the expression intensity was weaker than that of the normal control group. Conclusions:Electroacupuncture treatment of Taiyang (EX-HN5), Jingming (BL1), and Fengchi (GB21) acupoints can reactivate the plasticity of the visual cortex in adult amblyopic mice and improve their visual function.The mechanism may be related to the regulation of Nogo-A/NgR signaling pathway.

Objective:To investigate the effects of insulin-like growth factor 2 (IGF-2) on the expression of postsynaptic density protein 95 (PSD95), synaptophysin-1 (SYN1), and synaptophysin (SYP) in the mouse visual cortex and visual function after monocular deprivation (MD).Methods:Sixty-four SPF male Kunming mice aged 3 weeks were randomly divided into 4 groups: normal control group, MD group, MD+ IGF-2 recombinant protein (MD+ IGF-2) group, and MD+ fluoxetine (FLX) group, with 16 mice in each group.The MD group, MD+ IGF-2 group and MD+ FLX group were treated with right eyelid suturing at the beginning of 3 weeks old and eyelid opening at the end of 5 weeks old.The MD+ IGF-2 group was intraperitoneally injected with IGF-2 recombinant protein during MD.The MD+ FLX group was given fluoxetine via drinking water for 4 weeks after eyelid opening.The normal control group and MD group were injected intraperitoneally with bovine serum albumin every day from 3 to 5 weeks of age.At the end of 5 and 9 weeks of age, subjective visual function was evaluated by fore paw touching ground reflex experiment.At the end of 9 weeks of age, objective visual function was assessed by flash visual evoked potentials.After the mice were sacrificed, the left visual cortex of mice in each group was taken, and the expression of PSD95, SYN1, and SYP was assessed by Western blot.This study was approved by the Ethics Committee of Hunan Children's Hospital (No.HCHDWLL-2022-16). The handling of experimental animals was carried out in accordance with the Guidelines for the Management and Use of Laboratory Animals in Hunan Children's Hospital.Results:At the end of 5 and 9 weeks of age, there were overall significant differences in the success rate of fore paw touching ground among different groups of mice ( F=4.83, 3.36; both P<0.05). At the end of 5 weeks of age, the success rate was lower in MD group and MD+ FLX group than in normal control group, and significantly higher in MD+ IGF-2 group than in MD group, with statistically significant differences (all P<0.05). At the end of 9 weeks of age, the success rate was lower in MD group than in normal control group, and significantly higher in MD+ IGF-2 group and MD+ FLX group than in MD group (all P<0.05). There was a significant overall difference in P2 wave amplitude in F-VEP examination among different groups of mice ( F=13.99, P<0.01). The P2 wave amplitude was significantly lower in MD group than in normal control group and MD+ IGF-2 group (both P<0.01). There was no significant difference in the P2 wave latency of F-VEP among the four groups of mice ( F=2.83, P=0.07). The relative expression levels of PSD95, SYN1 and SYP proteins were 1.00±0.41, 1.00±0.10 and 1.00±0.27 in normal control group, 0.32±0.27, 0.68±0.20 and 0.56±0.28 in MD group, 0.78±0.32, 0.91±0.18 and 0.94±0.22 in MD+ IGF-2 group, 0.89±0.65, 0.98±0.28 and 0.94±0.47 in MD+ FLX group, respectively.There were significant differences in levels of PSD95, SYN1 and SYP in mice visual cortex among different groups ( F=4.24, 5.32, 3.40; all P<0.05). The expressions of PSD95, SYN1 and SYP proteins in the visual cortex were lower in MD group than in normal control group, and higher in MD+ IGF-2 group than in MD group (all P<0.05). Conclusions:Administration of exogenous IGF-2 to mice that underwent MD during the critical period can maintain visual cortex plasticity and protect the visual function to a certain extent.