ObjectiveTo investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease （COPD） and to analyze its possible mechanism of action. MethodsMale Sprague-Dawley （SD） rats were randomly divided into a normal group， an early COPD model group， an advanced COPD model group， an early-intervention high-dose group， a late-intervention high-dose group， an early-intervention low-dose group， a late-intervention low-dose group， an early-intervention pyrrolidine dithiocarbamate （PDTC） group， and a late-intervention PDTC group， with 15 rats in each group. A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide（LPS）， and a rat model of advanced COPD was constructed by using airway infusion with LPS， cigarette smoke， and hypoxia. All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment， smoked for 1 h per day， and administered the drug once a day for 40 weeks from day 15 onward. In the high- and low-dose groups， rats were given 1 g·kg^-1 and 250 mg·kg^-1 Qibai Pingfei capsules， respectively by gavage， and in PDTC groups， rats were given 100 mg·kg^-1 of PDTC by intraperitoneal injection. The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6. Lung function and mean pulmonary artery pressure were tested in rats. Morphologic changes in lung tissues were detected by hematoxylin-eosin（HE）staining. Collagen deposition in lung tissues was examined by Masson staining， and the levels of inflammatory factors including interleukin-1β（IL-1β）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α）in lung tissues were detected by enzyme-linked immunosorbent assay （ELISA）. The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining， and the protein expression of Toll-like receptor 4（TLR4）， myeloid differentiation factor 88（MyD88）， nuclear factor-κB（NF-κB）， TNF-α， vascular endothelial-cadherin（VE-cadherin）， α-smooth muscle actin（α-SMA）， and platelet endothelial cell adhesion molecule-1（CD31） was detected by Western blot in the lung tissues of rats. ResultsCompared with the normal group， the model group showed significantly decreased forced expiratory volume in 0.3 s （FEV_0.3）， forced vital capacity （FVC）， and FEV_0.3/FVC ratio related to lung function （P<0.05）， thickening of pulmonary vasculature， increased collagen deposition in the lungs， and enhanced mean pulmonary arterial pressure and expression levels of IL-6， IL-1β， and TNF-α （P<0.05）. Additionally， the model group also exhibited increased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， significantly higher protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05）， and significantly lower protein expression of VE-cadherin and CD31 （P<0.05）. Lung function was significantly improved in the Qibai Pingfei capsules groups compared with the model group （P<0.05）， with mean pulmonary arterial pressure reduced and pulmonary vascular thickening and collagen deposition in the lungs ameliorated. The Qibai Pingfei capsules groups also showed reduced expression levels of IL-6， IL-1β， and TNF-α （P<0.05） and decreased numbers of macrophages， lymphocytes， and neutrophils （P<0.05）， as well as reduced protein expression of TLR4， MyD88， NF-κB， TNF-α， and α-SMA （P<0.05） and elevated protein expression of VE-cadherin and CD31 （P<0.05） in rat lung tissues. ConclusionQibai Pingfei capsules inhibits inflammatory response and endothelial-to-mesenchymal transition probably by regulating the TLR4/NF-κB signaling pathway， thus improving pulmonary vascular remodeling in COPD model rats and showing therapeutic effects in the early stage of COPD.

Objective To establish a dual TaqMan probe-based qPCR method for determining the copy number of the geneti-cally modified pertussis toxin(PT) gene in detoxified pertussis vaccine strains, and to identify optimal reference genes forevaluating the genetic stability of modified strains during serial passage.MethodsSpecific primers and probes of modifiedgene PT and multiple housekeeping genes were designed. The optimal reference genes were screened by GeNorm, Norm-Finder, BestKeeper and Delta CT based on dual TaqMan probe qPCR. The copy number of PT gene of genetically detoxifiedpertussis vaccine strain was calculated by relative quantitative analysis. The specificity, linearity and repeatability of theestablished method were verified. The genomic DNA of P1, P3, P5, P10 and P15 strains used in the production of geneticallydetoxified pertussis vaccine was used as templates, and the passage stability of the strains was evaluated by using the estab-lished dual TaqMan probe qPCR method.ResultsThe stability of candidate reference genes was analyzed using GeNorm,NormFinder, BestKeeper, and Delta CT software, with Rpob identified as the most stable reference gene. Both the target PTgene and the reference Rpob gene were amplified in standard strain 58003. A good linear correlation(R~2≥ 0. 990) wasobserved between Ct values and template quantities within the concentration range of 0. 001 to 10 ng/μL. For P1 generationstrains, the 2~(-△△Ct)values from six replicate assays consistently ranged between 0. 87 and 1. 25, with an RSD of less than 20%.All tested generations exhibited single-copy PT target genes, demonstrating good genetic stability during serial passages.ConclusionThe established dual TaqMan probe qPCR assay demonstrates good primer specificity and reproducibility,making it suitable for evaluating the genetic stability of bacterial strains during serial passages in the production of geneti-cally detoxified pertussis vaccines, thereby further evaluating the quality of strains.

AIM: To investigate the relationship between the levels of serum dehydroepiandrosterone(DHEA), erythropoietin(Epo), vasohibin-1(VASH-1)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM). METHODS: Totally 185 T2DM patients(185 eyes)treated in our hospital from April 2021 to March 2024 were selected and divided into T2DM group(102 eyes)and DR group(83 eyes)based on whether retinal lesions occurred. DR patients were divided into nonproliferative DR group(NPDR, 47 cases, 47 eyes)and proliferative DR group(PDR, 36 cases, 36 eyes)based on the severity of their lesions. Fully automatic biochemical analyzer was used to detect serum biochemical indicators. ELISA was applied to detect serum levels of DHEA, Epo, and VASH-1. Pearson correlation was applied to analyze the correlation between serum DHEA, Epo, and VASH-1 levels and the severity of diabetic retinopathy. Logistic regression was applied to analyze the factors affecting the occurrence of DR. ROC curve was applied to analyze the diagnostic value of serum DHEA, Epo, and VASH-1 levels for T2DM combined with DR or PDR.RESULTS: Compared with the T2DM group, the DR group showed significantly increased DM duration, fasting blood glucose, uric acid, creatinine, and Epo, while DHEA and VASH-1 levels were significantly reduced(all P<0.05); Compared with the NPDR group, the PDR group showed a significant decrease in serum DHEA and VASH-1 levels, and a significant increase in Epo levels(all P<0.05); the levels of serum DHEA and VASH-1 were negatively correlated with the severity of DR, while the level of Epo was positively correlated with the severity of DR(all P<0.05); DHEA and VASH-1 were protective factors against DR, while Epo was a risk factor for DR(all P<0.05); the AUC of serum DHEA, Epo, and VASH-1 levels alone and in combination for the diagnosis of T2DM with DR were 0.804, 0.797, 0.805, and 0.903, respectively. The combined diagnostic value was higher than that of single diagnosis(all P<0.05); the AUC of serum DHEA, Epo, and VASH-1 levels alone and in combination for diagnosing PDR were 0.852, 0.850, 0.841, and 0.946, respectively. The value of combined diagnosis was significantly higher than that of individual diagnosis(all P<0.05).CONCLUSION:The levels of serum DHEA and VASH-1 in DR patients are clearly reduced, the level of Epo is clearly increased, and their levels are closely related to the severity of DR patients; therefore, combined detection has higher value for T2DM complicated with DR or PDR.

OBJECTIVES: The major histocompatibility complex class I chain-related gene A (MICA), a component of the human leukocyte antigen (HLA) gene complex, is involved in the pathogenesis of various diseases including cancers and autoimmune disorders. Rosacea, a chronic inflammatory skin disease with a complex pathogenesis, potentially influenced by genetic and autoimmune factors. This study aims to investigate the relationship among MICA gene polymorphisms, single nucleotide polymorphisms (SNPs), and susceptibility to rosacea, thereby offering new insights into the disease mechanism. METHODS: Peripheral blood DNA samples were collected from 84 patients with rosacea (rosacea group) and 223 healthy volunteers (control group) who visited the Dermatology Outpatient Department of Xiangya Hospital of Central South University between November 2017 and November 2019. MICA genotyping was performed using polymerase chain reaction-sequencing-based typing (PCR-SBT) and the next-generation sequencing (NGS), and the accuracy of the 2 methods was compared. The frequency distributions of MICA alleles between the 2 groups were analyzed. Amino acid clustering and SNP site analyses were conducted to identify haplotype-linked SNPs and to classify MICA polymorphic variants. Distribution differences of these classifications between groups were also examined. RESULTS: Blood tests in rosacea patients showed mildly elevated, with no significant changes in lymphocyte counts. Both PCR-SBT and NGS accurately identified MICA alleles. The most common alleles in the rosacea group were MICA*010:01, MICA*008:04, and MICA*019:01. The frequencies of MICA*002:01 and MICA*027 were significantly lower in the rosacea group compared to controls (6.55% vs 18.16% and 1.19% vs 5.38%, respectively), while and MICA*010:01 were significantly higher (7.74% vs 3.36% and 31.55% vs 18.61%, respectively; all P<0.05). Five short tandem repeat (STR) alleles were identified. Frequencies of MICA-A4 and MICA-A9 were lower in the rosacea group than in the control group (16.07% vs 23.32% and 7.74% vs 17.26%, respectively), whereas MICA-A6 was higher (10.12% vs 4.03%; all P<0.05). Clustering and SNP analysis identified 6 linked SNP sites, classifying MICA variants into Type I (C₃₆+M₁₂₉+K₁₇₃+G₂₀₆+W₂₁₀+S₂₁₅) and Type II (Y₃₆+V₁₂₉+E₁₇₃+S₂₀₆+R₂₁₀+T₂₁₅). Type I MICA variants were significantly associated with rosacea susceptibility. CONCLUSIONS MICA gene polymorphisms are associated with susceptibility to rosacea, and there are 6 linked SNP sites within the MICA gene. Based on this, MICA polymorphic variants are classified into Type I and Type II, with Type I being more closely associated with disease development of rosacea.
Humans ; Polymorphism, Single Nucleotide ; Histocompatibility Antigens Class I/genetics* ; Rosacea/genetics* ; Genetic Predisposition to Disease/genetics* ; Female ; Male ; Adult ; Middle Aged ; Genotype ; Alleles ; Gene Frequency ; Haplotypes ; Case-Control Studies ; Aged ; High-Throughput Nucleotide Sequencing

Objective:To retrospectively analyze the results of auditory examination,vestibular function examination and laboratory examination of 63 patients diagnosed as vestibular neuritis.Methods:A total of 63 patients diagnosed with vestibular neuritis hospitalized in the Department of Otolaryngology, Head and Neck Surgery of the Third Affiliated Hospital of Sun Yat-sen University, from October 2012 to December 2022 were recruited. All patients met the diagnostic criteria for the 2022 Bárány association vestibular neuritis. Clinical data and the results of pure tone audiometry, electrocochleogram, video electronystagmogram, caloric test, cervical vestibuloevoked myogenic potential（cVEMP）, ocular vestibuloevoked myogenic potential（oVEMP）, video head impulse test（vHIT） was collected.A total of 63 age-and sex-matched healthy subjects in the physical examination center were randomly selected as the control group. The differences of blood indexs and lipid metabolism indexes between the two groups were compared. Results:In patients with vestibular neuritis, 50 out of 63 patients presented normal threshold in pure tone audiometry, 8 out of 63 patients had bilateral high-frequency sensorineural hearing loss and 5 out of 63 patients had unilateral mild high-frequency sensorineural hearing loss, 56 out of 63 cases completed the electrocochleogram, of which 3 cases had a binaural-SP/AP amplitude ratio≥0.4, 5 cases had monaural amplitude ratio ≥0.4. Fifty-five out of 63 patients completed the caloric test with CP values greater than 30% in all. The ratio of patients completed cVEMP, oVEMP and vHIT were 46 cases, 22 cases and 30 cases, respectively. 17 out of 63 cases completed all the four vestibular function tests. According to these tests, 49 patients could determine the extent of injury，including 27 cases with unilateral superior vestibular nerve injury, 21 cases with unilateral superior and inferior vestibular nerve injury and 1 case with unilateral inferior vestibular nerve injury. There were significant differences in neutrophil value（P<0.001）, lymphocyte value（P<0.005）, neutrophil/lymphocyte ratio（P<0.001） and apolipoprotein A1（P<0.001） between patient group and control group. Inflammatory markers were risk factors for patients with vestibular neuritis. The OR values of neutrophil value and blood neutrophil/lymphocyte ratio were 1.81（1.38-2.37, P<0.001） and 2.11（1.41-3.16, P<0.001）, respectively. Apolipoprotein A1 was a protective factor for patients with vestibular neuritis, and the OR value was 0.004（0.001-0.042, P<0.001）. Conclusion:Electrocochleogram could be used in vestibular neuritis patients with normal pure tone threshold to test whether there is hidden hearing loss in these patients. Neutrophil value, lymphocyte value, neutrophil/lymphocyte ratio and apolipoprotein A1 were correlated with vestibular neuritis. The Neutrophil value and neutrophil/lymphocyte ratio were risk factors for morbidity.
Humans ; Vestibular Neuronitis/physiopathology* ; Retrospective Studies ; Female ; Male ; Audiometry, Pure-Tone ; Hearing Loss, Sensorineural/physiopathology* ; Middle Aged ; Adult ; Vestibular Function Tests ; Vestibular Evoked Myogenic Potentials ; Aged

Pediatric vertigo presents with complex etiologies, and its clinical diagnosis and management can be challenging due to children's limited ability to describe their symptoms. Recurrent vertigo episodes in children, who are at a critical stage of development, can readily lead to emotional disorders in both the children themselves and their guardians. This article reports a case of benign paroxysmal vertigo of childhood（BPVC） in a child who sought care from multiple providers. The child was found to have a patent foramen ovale（PFO） and mild emotional disorder. By analyzing challenges encountered during the diagnostic and management process in this case of recurrent pediatric vertigo, this study provides practical guidance for rational selection of diagnostic techniques and the comprehensive assessment of disease status in pediatric vertigo/dizziness.
Child ; Humans ; Affective Symptoms/complications* ; Foramen Ovale, Patent/complications* ; Vertigo/complications*

Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

Objective: To explore the network structure of dietary intake and physical fitness subtypes among junior and senior high school students, so as to provide precise and efficient intervention guidance for improving abnormal physical health issues in adolescents. Methods: Based on the 2020-2021 Database of Youth Health (DYH), a total of 9 730 junior and senior high school students in Shandong Province were included for analysis. Dietary intake was assessed using a modified Chinese Dietary Quality Questionnaire, and physical fitness was evaluated according to the "2014 National Student Physical Fitness Standard". The Kmeans clustering algorithm was employed to identify potential subtypes of physical fitness in junior and high school students. Network analysis was used to construct a network linking dietary intake and physical fitness symptoms and to identify clusters of dietary behaviors and physical fitness symptoms among adolescents of different genders. Results: The physical fitness among junior and senior high school students of different genders were categorized into two subtypes: the baseline steady type (3 427 male students, 4 039 female students) and the morphological deviation type (1 294 male students, 970 female students). Statistically significant differences were observed in network strength and network connectivity strength among different genders and physical fitness subtypes (all P<0.05). Connections between food intake and physical health symptom clusters across different genders and physical health types among junior and senior high school students were primarily achieved through instant noodle intake and physical fitness (males of morphological deviation type, weight=0.06), fruit intake and physical fitness (males of baseline steady type, weight=-0.07), potato intake and vital capacity (females of morphological deviation type, weight=0.09), and processed meat intake and vital capacity (females of baseline steady type, weight=0.05). Conclusions Dietary intake serves as a significant modifiable risk factor for the physical fitness of junior and high school students. Interventions should focus on promoting healthy eating habits.

Objective:To investigate the protective effect of lovastatin on liver injury in the rats induced by hyperlipidemia,and to elucidate its possible mechanism.Methods:Fifteen SD rats were randomly divided into control group,hyperlipidemia model group,and lovastatin group,with 5 rats in each group.The rats in control group were fed with standard diet,while the rats in hyperlipidemia model group and lovastatin group were fed high-fat diet for 12 weeks.Starting from the 8th week,the rats were administered treatments via gavage once a day for 4 weeks:the rats in lovastatin group received 2 mng·kg-1 lovastatin,while the rats in control group and hyperlipidemia model group received an equal volume of normal saline.The body weights of the rats in various groups were measured at weeks 1,8,9,10,11,and 12 after the experiment began;the histopathology of liver tissue of the rats in various groups was observed using HE staining;the serum levels of total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),malondialdehyde(MDA),as well as the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),and the levels of interleukin-2(IL-2),interleukin-6(IL-6),interleukin-12(IL-12),and tumor necrosis factor-a(TNF-α)of the rats in various groups were detected using commercial kits;the composition of the gut microbiota of the rats in various groups was analyzed by 16S rRNA sequencing.Results:Compared with control group,the body weight of the rats in hyperlipidemia model group was significantly increased from the 8th week of high-fat diet feeding(P＜0.05 or P＜0.01 or P＜0.001).Compared with hyperlipidemia model group,the body weight of the rats in lovastatin group was significantly decreased at weeks 11 and 12(P＜0.05).Compared with control group,the livers of the rats in hyperlipidemia model group appeared rough,pale,enlarged,with blunt edges,and had a granular and greasy texture.Compared with hyperlipidemia model group,the livers of the rats in lovastatin group were light brownish-red,soft,with slightly blunt edges,reduced volume,and less granularity and greasiness.Compared with control group,the liver cells of the rats in hyperlipidemia model group were swollen and disorganized,with pyknotic nuclei,extensive inflammatory cell infiltration,and numerous vacuolar degenerations.Compared with hyperlipidemia model group,the rats in lovastatin group showed significantly reduced hepatocyte swelling and degeneration,more orderly and intact liver cell arrangement,decreased inflammatory cell infiltration,and reduced vacuolar degeneration.Compared with control group,the serum levels of TC,TG,and LDL-C of the rats in hyperlipidemia model group were significantly increased(P＜0.05),and the serum HDL-C level was decreased(P＜0.05).Compared with hyperlipidemia model group,the serum levels of TC,TG,and LDL-C of the rats in lovastation group were significantly decreased(P＜0.05),and the serum HDL-C level was increased(P＜0.05).Compared with control group,the serum MDA levels and the ALT and AST activities of the rats in hyperlipidemia model group were significantly increased(P＜0.05),and the SOD and GSH-Px activities were significantly decreased(P＜0.05).Compared with hyperlipidemia model group,the serum MDA levels and ALT and AST activities of the rats in lovastatin group were decreased(P＜0.05),and the SOD and GSH-Px activities were increased(P＜0.05).Compared with control group,the serum levels of IL-2,IL-6,IL-12,and TNF-α of the rats in hyperlipidemia model group were significantly increased(P＜0.05).Compared with hyperlipidemia model group,the serum levels of IL-2,IL-6,IL-12,and TNF-α of the rats in lovastatin group were significantly decreased(P＜0.05).Compared with control group,the ACE and Chao1 indexes of the rats in hyperlipidemia model group were significantly decreased(P＜0.05).Compared with hyperlipidemia model group,the ACE and Chao1 indexes of the rats in lovastatin group were significantly increased(P＜0.05 or P＜0.01).Compared with control group,the relative abundances of Firmicutes and Proteobacteria of the rats in hyperlipidemia model group were significantly increased(P＜0.001),and the relative abundances of Bacteroidetes and Actinobacteria were decreased(P＜0.001).Compared with hyperlipidemia model group,the relative abundances of Firmicutes and Proteobacteria of the rats in lovastatin group were significantly decreased(P＜0.05 or P＜0.01),while the relative abundances of Bacteroidetes and Actinobacteria showed no significant changes.Compared with control group,the relative abundance of Lactobacillus of the rats in hyperlipidemia model group was significantly decreased(P＜0.001),and the relative abundances of Bacteroides,Desulfovibrio,and Clostridium were significantly increased(P＜0.01 or P＜0.001).Compared with hyperlipidemia model group,the relative abundance of Lactobacillus of the rats in lovastatin group showed no significant change but the relative abundances of Bacteroides,Desulfovibrio,and Clostridium were significantly decreased(P＜0.05 or P＜0.01 or P＜0.001).Conclusion:Lovastatin ameliorates liver injury induced by hyperlipidemia,and the mechanism may be related to its ability to improve gut microbiota composition and inhibit oxidative stress and inflammatory damage.