Amblyopia is a common visual development disorder and is the main cause of monocular vision impairment in children and adults. Photobiomodulation(PBM), a non-invasive treatment method, has gradually gained attention in the field of ophthalmology. This paper begins with the macroscopic manifestation of light on the animal model of amblyopia. Additionally, it discusses the pathological changes of the amblyopic retina and the human eye's central nervous system, as well as the influence and mechanism of PBM on the visual perception and processing system and its chemical effect on the visual system through dopamine and melatonin. It examines its mechanism of action, current clinical application status, and future development direction in order to provide new ideas and theoretical foundation for amblyopia treatment.

Objective Through integrative bioinformatics analysis of multi-source transcriptomic data, potential biomarkers to asthma epithelial cells were identified. The expression of these candidate target was subsequently validated in lung tissues and epithelial cells from asthma models. Methods The gene expression profile data of epithelial cells from three asthma patient cohorts and corresponding healthy controls were integrated from the Gene Expression Omnibus (GEO) database. Differential expression analysis and gene co-expression network analysis were performed to identify key genes and biological pathways associated with asthma. The key genes were validated in lung tissues and epithelial cells in asthma animal models. Results Differential gene expression analysis revealed 1121 upregulated and 1484 downregulated genes in epithelial cells from asthma patients compared with healthy controls. The biological pathway enrichment analysis revealed that the upregulated genes were mainly involved in glycosylation processes, whereas the downregulated genes were mainly associated with immune cell differentiation process. The gene co-expression network analysis revealed that module 9, enriched in glycosylation-related pathways, was significantly positively correlated with asthma, whereas module 17, associated with insulin and other signaling pathways, showed a significant negative correlation with asthma. We identified the genes of polypeptide N-acetylgalactosaminyltransferase 5 (GALNT5), pyrroline-5-carboxylate reductase 1 (PYCR1), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as key genes within module 9, all of which were significantly upregulated in asthma. Finally, we validated that the expression levels of GALNT5, PYCR1, and CEACAM5 were significantly upregulated in epithelial cells from asthmatic lung tissue. Additionally, using a rat asthma model, we further confirmed that the protein levels of these three genes were significantly upregulated in lung tissues of the model group. Conclusion Through data integration and experimental validation, this study identified key genes and biological pathways closely associated with asthma pathogenesis. These findings provide a novel theoretical basis and potential targets for the diagnosis and treatment of asthma.
Asthma/metabolism* ; Humans ; Epithelial Cells/metabolism* ; Animals ; Biomarkers/metabolism* ; Gene Expression Profiling ; Transcriptome ; Gene Regulatory Networks ; Rats ; Computational Biology

OBJECTIVE: Paridis Rhizoma (Chonglou in Chinese), a traditional Chinese herbal medicine, has been shown have strong anti-tumor effects. Paris saponin VII (PSVII), an active constituent isolated from Paridis Rhizoma, was demonstrated to significantly suppress the proliferation of BxPC-3 cells in our previous study. Here, we aimed to elucidate the anti-pancreatic ductal adenocarcinoma (PDAC) effect of PSVII and the underlying mechanism. METHODS: Cell viability was determined by CCK-8, colony formation, and cell migration assays. Cell apoptosis and reactive oxygen species (ROS) production were measured by flow cytometry with annexin V/propidine iodide (Annexin V/PI) and 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), respectively. Pyroptosis was evaluated by morphological features, Hoechst 33342/PI staining assay, and release of lactate dehydrogenase (LDH). JC-1 fluorescent dye was employed to measure mitochondrial membrane potential. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the levels of proteins or mRNAs. The effect in vivo was assessed by a xenograft tumor model. RESULTS: PSVII inhibited the viability of PDAC cells (BxPC-3, PANC-1, and Capan-2 cells) and induced gasdermin E (GSDME) cleavage, as well as the simultaneous cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP). Knockdown of GSDME shifted PSVII-induced pyroptosis to apoptosis. Additionally, the effect of PSVII was significantly attenuated by Z-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone (Z-DEVD-FMK), on the induction of GSDME-dependent pyroptosis. PSVII also elevated intracellular ROS accumulation and stimulated Bax and Caspase-3/GSDME to conduct pyroptosis in PDAC cells. The ROS scavenger N-acetyl cysteine (NAC) suppressed the release of LDH and inhibited Caspase-9, Caspase-3, and GSDME cleavage in PDAC cells, ultimately reversing PSVII-induced pyroptosis. Furthermore, in a xenograft tumor model, PSVII markedly suppressed the growth of PDAC tumors and induced pyroptosis. CONCLUSION These results demonstrated that PSVII exerts therapeutic effects through Caspase-3/GSDME-dependent pyroptosis and may constitute a novel strategy for preventing chemotherapeutic resistance in patients with PDAC in the future.

This article reports a patient with hepatic coma who underwent artificial liver support therapy and liver transplantation successfully， and the patient recovered well in the later stage after active treatment. This article also discusses the timing of liver transplantation.

Objective: To discuss the clinical value of neck circumference in screening for overweight and obesity in children and adolescents, so as to provide a theoretical basis and new ideas for overweight and obesity screening. Methods: From May to July 2023, a total of 2 493 children and adolescents aged 3 to 16 were sampled from three schools by the cluster random sampling method. General data, neck circumference, body mass index (BMI), waisttoheight ratio, and other information were collected. Mann-Whitney ranksum test, Spearman correlation analysis, and receiver operating characteristic (ROC) curve analysis were used to statistically analyze the data. Results: The prevalence of overweight and obesity in children and adolescents aged 3 to 16 was 33.05%, and the prevalence of abdominal obesity was 28.33%.The neck circumferences of boys and girls in the overweight and obese group showed statistically significant differences from the normal weight group during the preschool, schoolage, and adolescence periods (Z=-16.69--4.54, P<0.05). The neck circumferences of children of different genders were moderately positively correlated with BMI (r=0.50-0.79, P<0.01). ROC curve analysis showed that neck circumference had good accuracy in assisting the screening for the occurrence of overweight and obesity in boys and girls during the preschool, schoolage, and adolescence periods [the AUC for boys:0.80(0.71-0.89), 0.89(0.86-0.91), 0.84(0.81-0.87); the AUC for girls:0.76(0.67-0.86), 0.81(0.74-0.88), 0.73(0.68-0.77), P<0.01], the optimal neck circumference cutoff values for boys were 26.95, 28.95, 33.55 cm, and for girls were 25.05, 26.55, 28.35 cm respectively. The neck circumferences of boys and girls were moderately positively correlated with the waisttoheight ratio during the schoolage and adolescence periods (r=0.41-0.70, P<0.01). ROC curves showed that neck circumferences had good accuracy in assisting the screening for the occurrence of abdominal obesity in boys and girls during the schoolage and adolescence periods [the AUC for boys:0.89(0.86-0.92), 0.82(0.78-0.85); the AUC for girls:0.84(0.75-0.93), 0.87(0.75-0.93)], the optimal cutoff values for boys were 28.95, 32.75 cm; for girls were 26.45, 31.85 cm respectively. Conclusion The neck circumference can be applied to screen for overweight and abdominal obesity in children and adolescents, and can provide new ideas for the prevention and control of overweight and obesity in children and adolescents.

Objective:To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA) who failed anti-retroviral therapy (ART) in Henan Province, in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods:PLWHA with virological failure (human immunodeficiency virus (HIV) RNA≥500 copies/mL) after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022. Baseline CD4 + T lymphocyte counts, ART regimens and other clinical data were collected. HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People′s Hospital of Zhengzhou, and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results. Genotypic drug resistance to nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase inhibitors (INSTI) was determined. Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure. Results:Among 982 PLWHA, the sequences of 899 cases were successfully amplified, and drug resistance was detected in 737 cases, with the drug resistance rate of 81.98%(737/899). The rates of resistance to NRTIs, NNRTIs, PIs and INSTIs were 71.97%(647/899), 79.31%(713/899), 5.23%(47/899) and 2.72%(20/734), respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases (79.78%), mainly NRTI and NNRTI concomitant resistance in 583 cases (79.10%). There were 99 cases (13.43%) who developed resistance to only one class of drugs, and those who developed concurrent resistance to three classes of drugs were 48 cases (6.51%), and two cases (0.27%) were found to be resistant to all four classes of drugs mentioned above. A total of 10 HIV genotypes were detected, among which subtype B accounted for the most (59.73%(537/899)), followed by circulating recombinant form (CRF)01_AE subtype (21.91%(197/899)) and CRF07_BC subtype (9.45%(85/899)). The risk factors affecting the development of drug resistance were baseline CD4 + T lymphocyte counts, ART regimens and HIV-1 genotypes. The risk of drug resistance in patients with baseline CD4 + T lymphocyte counts <100/μL was 4.55 times (95% confidence interval ( CI) 2.69 to 7.70) higher than patients with CD4 + T lymphocyte counts≥250/μL, the risk of drug resistance in patients using 2NRTIs+ NNRTI regimen was 4.51 times (95% CI 1.75 to 11.63) higer than those using 2NRTIs+ INSTI regimen, and patients infected with B and CRF01_AE subtype was 2.18 times (95% CI 1.10 to 4.29) and 2.70 times (95% CI 1.26 to 5.78) higer than those with CRF07_BC subtype, respectively. Conclusions:The incidence of genotypic drug resistance in PLWHA with ART failure in Henan Province is high. Low baseline CD4 + T lymphocyte counts, 2NRTIs+ NNRTI regimens, and genotype B and CRF01_AE are risk factors for drug resistance in PLWHA.

Objective To investigate the protective effect of metformin against PM2.5-induced functional impairment of placental trophoblasts and explore the underlying mechanism.Methods Sixteen pregnant Kunming mice were randomly assigned into two groups(n=8)for intratracheal instillation of PBS or PM2.5 suspension at 1.5,7.5,and 12.5 days of gestation.The pregnancy outcome of the mice was observed,and placental zonal structure and vascular density of the labyrinth area were examined with HE staining,followed by detection of ferroptosis-related indexes in the placenta.In cultured human trophoblasts(HTR8/SVneo cells),the effects of PM2.5 exposure and treatment with metformin on cell viability,proliferation,migration,invasion,and tube formation ability were evaluated using CCK8 assay,EDU staining,wound healing assay,Transwell experiment,and tube formation experiment;the cellular expressions of ferroptosis-related proteins were analyzed using ELISA and Western blotting.Results M2.5 exposure of the mice during pregnancy resulted in significantly decreased weight and number of the fetuses and increased fetal mortality with a reduced placental weight(all P<0.001).PM2.5 exposure also caused obvious impairment of the placental structure and trophoblast ferroptosis.In cultured HTR8/SVneo cells,PM2.5 significantly inhibited proliferation,migration,invasion,and angiogenesis of the cells by causing ferroptosis.Metformin treatment obviously attenuated PM2.5-induced inhibition of proliferation,migration,invasion,and angiogenesis of the cells,and effectively reversed PM2.5-induced ferroptosis in the trophoblasts as shown by significantly increased intracellular GSH level and SOD activity,reduced MDA and Fe2+ levels,and upregulated GPX4 and SLC7A11 protein expression(P<0.05 or 0.01).Conclusion PM2.5 exposure during pregnancy causes adverse pregnancy outcomes and ferroptosis and functional impairment of placental trophoblasts in mice,and metformin can effectively alleviate PM2.5-induced trophoblast impairment.

Background::Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP.Methods::We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia. Results::mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485. Conclusion::High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.

Objective To investigate the effect and mechanism of Nuanxinkang on plaque formation in obstructive sleep apnea-hypopnea syndrome(OSAHS)comorbid with atherosclerosis(AS)mice by inhibiting endothelial-to-mesenchymal transition(EndMT).Methods Male ApoE-/-mice were randomly divided into six groups:control group,model group,atorvastatin group(2.6 mg·kg-1)and Nuanxinkang low-,medium-and high-dose groups(crude drug 3.5,7.0,14.0 g·kg-1),with eight mice in each group.The mice were exposed to chronic intermittent hypoxia(CIH)environment during sleep for a long time,and fed with high-fat diet to replicate OSAHS comorbid with AS mouse model.Oil red O staining was used to observe the formation of plaque on aortic intima in mice.Masson trichrome staining was used to evaluate the collagen content of atherosclerotic plaques in the aortic root of mice.The expressions of endothelial cell marker CD31 and EndMT marker Vimentin in aortic plaque were detected by immunofluorescence.Blood lipid levels were determined by ELISA;the mRNA expression levels of EndMT markers α-SMA and Cdh2 in aortic tissue were detected by qPCR.Results Compared with the control group,the area of aortic atherosclerotic plaque in the model group was significantly increased(P＜0.01),and the area of collagen deposition in the aortic root plaque was significantly increased(P＜0.01).The number of CD31 positive cells in the plaque were significantly decreased(P＜0.01),and the number of Vimentin positive cells were significantly increased(P＜0.01).Serum TG,T-CHO and LDL-C levels were significantly increased(P＜0.01),and HDL-C level was significantly decreased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue were significantly increased(P＜0.01).Compared with the model group,the area of aortic atherosclerotic plaque in Nuanxinkang groups were significantly reduced(P＜0.05,P＜0.01),and the collagen deposition area of aortic root atherosclerotic plaque were significantly reduced(P＜0.05,P＜0.01).The number of CD31 positive expression cells in the plaque of Nuanxinkang high-dose group were significantly increased(P＜0.05),and the number of Vimentin positive expression cells in the plaque of Nuanxinkang medium-and high-dose groups were significantly decreased(P＜0.05,P＜0.01).The serum TG level of mice in the high-dose group of Nuanxinkang was significantly decreased(P＜0.01).The serum T-CHO and LDL-C levels of mice in each Nuanxinkang administration group were significantly decreased(P＜0.05,P＜0.01).The serum HDL-C levels of mice in the medium-and high-dose groups of Nuanxinkang were significantly increased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue of mice in each treatment group were significantly decreased(P＜0.01).Conclusion Nuanxinkang can effectively reduce the plaque formation in OSAHS comorbid with atherosclerosis mice,which may be related to its inhibition of EndMT and reduction of collagen fiber formation.

Objective The purpose of this study was to investigate the application value of Chromosomal microarray analysis(CMA)in prenatal diagnosis of nuchal translucency(NT)thickening and nasal bone dyscalci-fication.Methods The fetuses diagnosed with NT thickening and nasal bone dyscalcification at the Prenatal Diagnosis Center of Meizhou People's Hospital from September 2022 to April 2024,who underwent CMA and karyotype analysis were collected to analyze the relationship between NT thickening and nasal bone dyscalcification and chromosome abnormalities.The detection of chromosomal abnormalities in fetuses with NT thickening,nasal bone dyscalcification and the value of ultrasound combined with CMA in prenatal diagnosis were analyzed.Results In 75 fetuses with NT thickening and/or nasal bone dyscalcification,11 cases of chromosome aneuploidy were detected by karyotype analysis,and 5 cases of pathogenic copy number variations(CNV)were detected by CMA,with an additional detection rate of 6.7%.The additional diagnosis rates of CMA were 6.0%and 5.0%in fetuses with simple NT thickening and nasal bone dyscalcification,respectively.Conclusion CMA technique is of high value in prenatal diagnosis of fetuses with NT thickening and nasal bone dyscalcification,it can improve the detec-tion rate of fetal chromosomal abnormalities,and the combined application of multiple techniques can provide a more comprehensive evaluation of the fetuses.