Objective:To assess the status of undernutrition and appropriate catch-up growth in extremely preterm infants within 24 months of corrected age (CA).Methods:A retrospective cohort study was conducted. A total of 422 extremely preterm infants born at Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University from January 2017 to December 2022 and followed up until 24 months of CA were enrolled. The extremely preterm infants were grouped by gestational age at birth (<25, 25-26, 27 weeks), birth weight (<500, 500-749, 750-999,≥1 000 g), weight for gestational age (large for gestational age (LGA), appropriate for gestational age (AGA), small for gestational age (SGA)) and sex. Weight data within 24 months of CA were collected every 3 months. Nutritional insufficiency, growth rate, and achievement of adequate catch-up growth were analyzed during the period from 0 to 24 months of CA. Z-score method was used to analyze data. Fenton 2013 preterm growth charts (Fenton 2013) were used before 40 weeks of corrected gestational age, and World Health Organization child growth standards (2009) fitted Z-scores were applied from 40 weeks of CA. Changes in weight Z-scores of extremely preterm infants from 0 to 24 months of CA were observed and compared, the occurrence of moderate to severe malnutrition and growth retardation was determined, nutritional insufficiency was assessed, and growth rate as well as the achievement of appropriate catch-up growth were analyzed. The Lambda-mu-sigma method combined with the Z-score fitting model was used to fit and analyze the distribution characteristics of weight percentiles in extremely preterm infants. The Chi-square test was used to compare differences among groups.Results:A total of 422 extremely preterm infants were included, with a gestational age at birth of 26.3(25.4, 27.2) weeks and a birth weight of (880±177) g. Among them, 238 were males and 184 were females; 36 cases (8.5%) were LGA, and 16 cases (3.8%) were SGA. During follow-up within 24 month of CA, 89 cases (21.1%) developed moderate to severe malnutrition. When compared separately among different birth weight and gestational age at birth groups, there had both statistically differences in the incidence of moderate to severe malnutrition ( χ2=42.94 and 9.17, both P<0.05). The incidence was the highest in the birth weight of CA<500 g group and the <25 weeks gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks gestational age at birth group in their respective groups. Growth retardation occurred in 5.2% (22/422). However, there had statistically differences in the incidence of growth retardation among different birth weight and gestational age at birth groups, in each grouped time interval ( χ2=21.61 and 4.30, both P<0.05). The proportions of rapid growth were relatively high in the 0-3 months and 3-6 months of CA groups, which were 96 cases (27.4%) and 98 cases (26.6%), respectively. Overall, appropriate catch-up growth was achieved in 341 cases (80.8%) from 0 to 24 months of CA. There had statistically differences in the completion rate of appropriate catch-up growth among different birth weight and gestational age at birth groups ( χ2=23.65 and 7.08, both P<0.05). The completion rate was the highest in the birth weight of CA<500 g group and the <25 weeks of gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks of gestational age at birth group. Conclusions:The lower the birth weight and gestational age of extremely preterm infants, the higher the incidence of moderate to severe malnutrition and the lower the achievement rate of adequate catch-up growth within 24 months of CA. The period of 0-6 months of CA is the critical window for catch-up in extremely preterm infants.

Objective: To evaluate the classroom environmental management and CO 2 volume concentration in primary and secondary schools from Liaoning, Tianjin, and Shanghai, thereby providing a scientific basis for developing targeted strategies to improve classroom air quality. Methods: From December 16 to 26, 2024, by using stratified random cluster sampling method, the questionnaire survey was conducted in 72 primary and secondary schools (24 each of primary, junior high, and regular high schools) across Liaoning, Tianjin and Shanghai. Information on heating, ventilation and other classroom environmental management was collected. Additionally, 108 classrooms were selected for on site microclimate measurements, including temperature, humidity, wind speed and CO 2 volume concentration. Univariate analysis and multiple linear regression models were employed to explore related factors of classroom CO 2 volume concentration. Results: Among the three provinces/municipalities, 20.8% of schools regularly monitored the microclimate. The overall compliance rate for classroom CO 2 volume concentration was 17.6%. Multiple linear regression analysis showed that CO 2 volume concentration in regular and junior high school classrooms were higher than in primary school classrooms ( β=0.067, 0.046, 95%CI =0.036-0.099, 0.013-0.080); classrooms ventilated regularly in the morning and afternoon had higher CO 2 volume concentration than those ventilated during every break between classes ( β=0.043, 95%CI = 0.007- 0.080); both temperature ( β=0.010, 95%CI =0.004-0.016) and humidity ( β=0.003, 95%CI =0.002-0.004) were positively correlated with CO 2 volume concentration (all P <0.05). Conclusions Excessive CO 2 volume concentration in primary and secondary school classrooms is a prominent issue, and ventilation frequency is a key intervenable factor for controlling CO 2 levels. It is recommended to promote ventilation during every break between classes as a core management measure and to emphasize air quality supervision in regular high school classrooms.

ObjectiveTo investigate the effect of the Buyang Huanwutang （BHT）-containing serum on the bleomycin-induced senescence of A549 cells and explore the potential mechanism by which BHT ameliorates pulmonary fibrosis. MethodsA549 cells were cultured in vitro and modeled for senescence through the application of bleomycin. SD rats were administrated with BHT by gavage for the preparation of BHT-containing serum， and the effect of BHT-containing serum on the viability of the cell model was studied through a cell experiment designed with the following groups： blank group， model group， 2.5%， 5%， and 10% BHT-containing serumgroups. The effect of BHT-containing serum on the BLM-induced senescence of A549 cells was studied by the experiment designed with blank group， model group， positive group （PC，pirfenidone，600 mg·L^-1）， 2.5%， 5%， 10% BHT-containing serum groups. SA-β-Gal staining was used to reveal the area of senescence-positive cells， and flow cytometry was employed to analyze the cell cycle distribution. Real-time PCR and the immunofluorescence assay were adopted to determine the mRNA and protein levels of cell senescence markers p16 and p21. Western blot was employed to quantify the protein levels of senescence-associated secretory phenotype （SASP） molecules interleukin （IL）-1β， IL-6， matrix metalloproteinase （MMP）-3， chemokine ligand （CCL）2， tumor necrosis factor （TNF）-α， and transforming growth factor-β （TGF-β）/Smad pathway molecules TGF-β₁， Smad2， phosphorylated （p）-Smad2， Smad3， and p-Smad3. ResultsCompared with the blank group， the model group showed a decrease in cell survival rate （P<0.01）， increases in the SA-β-Gal-positive area， the proportion of cells in G₀/G₁ phase， the mRNA and protein levels of P16 and P21， and the protein levels of IL-1β， IL-6， TNF-α， MMP-3， CCL2， TGF-β₁， p-Smad2， and p-Smad3 （P<0.05，P<0.01）. Compared with the model group， the BHT-containing serum at each dose increased the cell survival rate （P<0.01） and decreased the SA-β-Gal-positive area， the proportion of cells in G₀/G₁ phase， the mRNA and protein levels of p16 and p21， and the protein levels of IL-1β， IL-6， TNF-α， MMP-3， and CCL2 （P<0.05， P<0.01）. Moreover， the inhibitory effect of BHT-containing serum on cell senescence showed a dose-dependent manner， with the 10% BHT-containing serum showing the most obvious effects and inhibiting the expression of TGF-β₁， p-Smad2， and p-Smad3 （P<0.01）. The effect of 10% BHT-containing serum was comparable to that of pirfenidone， and the serum even outperformed pirfenidone in inhibiting the expression of TNF-α and Smad2 （P<0.05）. ConclusionThe BHT-containing serum can inhibit BLM-induced senescence of A549 cells in a dose-dependent manner by regulating the TGF-β/Smad signaling pathway.

Objective:To assess the status of undernutrition and appropriate catch-up growth in extremely preterm infants within 24 months of corrected age (CA).Methods:A retrospective cohort study was conducted. A total of 422 extremely preterm infants born at Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University from January 2017 to December 2022 and followed up until 24 months of CA were enrolled. The extremely preterm infants were grouped by gestational age at birth (<25, 25-26, 27 weeks), birth weight (<500, 500-749, 750-999,≥1 000 g), weight for gestational age (large for gestational age (LGA), appropriate for gestational age (AGA), small for gestational age (SGA)) and sex. Weight data within 24 months of CA were collected every 3 months. Nutritional insufficiency, growth rate, and achievement of adequate catch-up growth were analyzed during the period from 0 to 24 months of CA. Z-score method was used to analyze data. Fenton 2013 preterm growth charts (Fenton 2013) were used before 40 weeks of corrected gestational age, and World Health Organization child growth standards (2009) fitted Z-scores were applied from 40 weeks of CA. Changes in weight Z-scores of extremely preterm infants from 0 to 24 months of CA were observed and compared, the occurrence of moderate to severe malnutrition and growth retardation was determined, nutritional insufficiency was assessed, and growth rate as well as the achievement of appropriate catch-up growth were analyzed. The Lambda-mu-sigma method combined with the Z-score fitting model was used to fit and analyze the distribution characteristics of weight percentiles in extremely preterm infants. The Chi-square test was used to compare differences among groups.Results:A total of 422 extremely preterm infants were included, with a gestational age at birth of 26.3(25.4, 27.2) weeks and a birth weight of (880±177) g. Among them, 238 were males and 184 were females; 36 cases (8.5%) were LGA, and 16 cases (3.8%) were SGA. During follow-up within 24 month of CA, 89 cases (21.1%) developed moderate to severe malnutrition. When compared separately among different birth weight and gestational age at birth groups, there had both statistically differences in the incidence of moderate to severe malnutrition ( χ2=42.94 and 9.17, both P<0.05). The incidence was the highest in the birth weight of CA<500 g group and the <25 weeks gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks gestational age at birth group in their respective groups. Growth retardation occurred in 5.2% (22/422). However, there had statistically differences in the incidence of growth retardation among different birth weight and gestational age at birth groups, in each grouped time interval ( χ2=21.61 and 4.30, both P<0.05). The proportions of rapid growth were relatively high in the 0-3 months and 3-6 months of CA groups, which were 96 cases (27.4%) and 98 cases (26.6%), respectively. Overall, appropriate catch-up growth was achieved in 341 cases (80.8%) from 0 to 24 months of CA. There had statistically differences in the completion rate of appropriate catch-up growth among different birth weight and gestational age at birth groups ( χ2=23.65 and 7.08, both P<0.05). The completion rate was the highest in the birth weight of CA<500 g group and the <25 weeks of gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks of gestational age at birth group. Conclusions:The lower the birth weight and gestational age of extremely preterm infants, the higher the incidence of moderate to severe malnutrition and the lower the achievement rate of adequate catch-up growth within 24 months of CA. The period of 0-6 months of CA is the critical window for catch-up in extremely preterm infants.

ObjectiveTo establish a model that can quickly identify the aroma components in different parts of Nardostachys jatamansi， so as to provide a quality control basis for the market circulation and clinical use of N. jatamansi. MethodsHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） combined with Smart aroma database and National Institute of Standards and Technology（NIST） database were used to characterize the aroma components in different parts of N. jatamansi， and the aroma components were quantified according to relative response factor（RRF） and three internal standards， and the markers of aroma differences in different parts of N. jatamansi were identified by orthogonal partial least squares-discriminant analysis（OPLS-DA） and cluster thermal analysis based on variable importance in the projection（VIP） value >1 and P<0.01. The odor data of different parts of N. jatamansi were collected by Heracles Ⅱ Neo ultra-fast gas phase electronic nose， and the correlation between compound types of aroma components collected by the ultra-fast gas phase electronic nose and the detection results of HS-SPME-GC-MS was investigated by drawing odor fingerprints and odor response radargrams. Chromatographic peak information with distinguishing ability≥0.700 and peak area≥200 was selected as sensor data， and the rapid identification model of different parts of N. jatamansi was established by principal component analysis（PCA）， discriminant factor alysis（DFA）， soft independent modeling of class analogies（SIMCA） and statistical quality control analysis（SQCA）. ResultsThe HS-SPME-GC-MS results showed that there were 28 common components in the underground and aboveground parts of N. jatamansi， of which 22 could be quantified and 12 significantly different components were screened out. Among these 12 components， the contents of five components（ethyl isovalerate， 2-pentylfuran， benzyl alcohol， nonanal and glacial acetic acid，） in the aboveground part of N. jatamansi were significantly higher than those in the underground part（P<0.01）， the contents of β-ionone， patchouli alcohol， α-caryophyllene， linalyl butyrate， valencene， 1，8-cineole and p-cymene in the underground part of N. jatamansi were significantly higher than those in the aboveground part（P<0.01）. Heracles Ⅱ Neo electronic nose results showed that the PCA discrimination index of the underground and aboveground parts of N. jatamansi was 82， and the contribution rates of the principal component factors were 99.94% and 99.89% when 2 and 3 principal components were extracted， respectively. The contribution rate of the discriminant factor 1 of the DFA model constructed on the basis of PCA was 100%， the validation score of the SIMCA model for discrimination of the two parts was 99， and SQCA could clearly distinguish different parts of N. jatamansi. ConclusionHS-SPME-GC-MS can clarify the differential markers of underground and aboveground parts of N. jatamansi. The four analytical models provided by Heracles Ⅱ Neo electronic nose（PCA， DFA， SIMCA and SQCA） can realize the rapid identification of different parts of N. jatamansi. Combining the two results， it is speculated that terpenes and carboxylic acids may be the main factors contributing to the difference in aroma between the underground and aboveground parts of N. jatamansi.

ObjectiveTo investigate the inhibitory effect of Huoluo Xiaolingdan on triple negative breast cancer （TNBC） in mice through its regulation of TCF1⁺CD8⁺ stem cell-like T cells infiltration. MethodsA mouse model of TNBC was established and the mice were randomly divided into the model group， low-dose （3.9 g·kg^-1）， medium-dose （7.8 g·kg^-1） and high-dose （15.6 g·kg^-1） Huoluo Xiaolingdan groups， and anti-PD-1 antibody treatment group. Each group was given a dose of 0.01 mL·g^-1， while the model group and the anti-PD-1 treatment group were also given an equivalent volume of normal saline. The drug was administered for 21 days. In the anti-PD-1 antibody group， mice were intraperitoneally injected with 100 μg of mouse anti-PD-1 antibody twice a week， for a total of five injections. The tumor volume， survival time and tumor mass were measured at different time points. Hematoxylin-eosin （HE） staining was used to observe the histological changes of the tumor. The expression of CD8⁺T cells and TCF1⁺CD8⁺ stem-like T cells in tumor tissues was detected by immunohistochemistry and immunofluorescence staining. Flow cytometry was used to detect the difference of immune cell subsets in tumors and the expression difference of TCF1⁺CD8⁺ stem cell-like T cells in tumors and peripheral blood. The expression level of PD-L1 in tumor tissues was detected by Western blot. ResultsCompared with model group， the tumor volume and mass of in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group were decreased （P<0.05， P<0.01）. The median survival time of mice in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was as follows： 27.00 days （95%CI， 0.45-2.65）， 31.00 days （95%CI， 0.32-1.89）， 34.00 days （95%CI， 0.40-2.33）， and 35.00 days （95%CI， 0.42-2.47）. All of them were higher than that of the model group ［24.50 days （95%CI， 0.37-10.5）］. Flow cytometry showed that compared with the model group， the proportion and number of infiltrating CD8⁺ T cells in tumor were increased in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group （P<0.05， P<0.01）， while the proportion of tumor regulatory T cells （Treg） and M2 macrophages decreased （P<0.05）. Compared with the model group， the proportion of IFN-γ⁺CD8⁺ T and GrzB⁺CD8⁺ T cells in tumors in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was increased （P<0.01）， and the proportion of TCF1⁺CD8⁺ T cells in tumor and peripheral blood was also increased. Immunofluorescence staining further showed that the number of TCF1⁺CD8⁺ T cells in tumor tissues increased in low-， medium- and high-dose Huoluo Xiaolingdan groups. Western blot analysis showed no significant decrease in the PD-L1 protein expression in tumor tissues between the Huoluo Xiaolingdan groups and the model group. ConclusionHuoluo Xiaolingdan can inhibit TNBC in mice by increasing tumor infiltration of TCF1⁺CD8⁺ stem-like T cells， enhancing CD8⁺ T cell activity， and regulating immune cell subgroups such as M2 macrophages and Treg cells to enhance anti-tumor immunity. This study provides a theoretical basis for the clinical application of Huoluo Xiaolingdan in breast cancer treatment and combination therapy.

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Objective: To understand the home reading-writing levels among children and adolescents in Shanghai after school, and to explore its association with screening myopia, so as to provide a scientific basis for the prevention and control of myopia. Methods: From April to December 2024, 641 primary and middle school students were recruited from 2 urban schools and 1 rural school in Shanghai to participate in the survey. An illuminance meter was used to measure the illuminance of home reading-writing activities after school. Screening myopia was determined through visual acuity examination and refractive detection under non ciliary muscle paralysis conditions among children and adolescents. A binary Logistic regression model was used to analyze the association between home reading-writing illuminance and screening myopia. Results: The detection rate of screening myopia among children and adolescents in Shanghai was 59.9%. The median home reading-writing illuminance after school was 340.9(112.2, 753.5) lx, and 45.4% was found of less than 300 lx. The family illuminance in the primary school stage [432.0 (136.9, 837.0) lx] was higher than that in the junior high school stage [113.1(53.7, 375.1) lx], and main urban area group [503.9 (212.6, 969.5) lx] was higher than that in the rural group [141.6 (53.7, 416.9) lx], the differences were statistically significant (Z=-7.56, -9.95,both P<0.05). The results of Logistic regression analysis showed that compared with the family illuminance of 150-500 lx, children and adolescents with family illuminance<150 and >500 lx had increased risks of screening myopia detection[OR(95%CI)=1.56(1.01-2.42), 1.74(1.15-2.62),both P<0.05]. Conclusions The home reading-writing illuminance after school is suboptimal. Both excessively low and high home reading-writing illuminance levels are associated with screen-detected myopia. It is necessary for children and adolescents to improve lighting conditions during evening reading-writing activities, and strengthen health education according to different regions and school stages.