Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Primary biliary cholangitis （PBC） is a chronic progressive autoimmune liver disease that is often comorbid with other connective tissue diseases （CTDs）， and such comorbidity can significantly alter the natural course or clinical phenotype of PBC or CTDs， limiting available therapeutic drugs and complicating clinical decision-making. Due to the involvement of the interdisciplinary subjects of hepatology， rheumatology， and clinical immunology and a paucity of large-scale cohort data and in-depth basic research， there is a limited understanding of such comorbidity in clinical practice， which increases the complexity of clinical diagnosis and treatment. This article summarizes the comorbidity of PBC with common CTDs such as Sjögren’‍s syndrome， systemic sclerosis， systemic lupus erythematosus， and idiopathic inflammatory myopathies， and analyzes related immune mechanisms， clinical manifestations， diagnostic challenges， treatment strategies， and prognosis. It is expected to establish PBC-CTD comorbidity cohorts through future multidisciplinary collaborations， focus on genetic background， immune mechanisms， and multi-omics approaches， elucidate pathogenesis and novel therapeutic targets， and improve the prognosis of patients by optimizing treatment strategies through precision medicine and artificial intelligence.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

This paper reported a patient with early-onset Alzheimer's disease （AD） who had previously responded poorly to anti-dementia medications while showed improvement in cognitive functioning after treatment with occupational therapy and computerized cognitive remediation therapy （CCRT） for 50 minutes three times per week. This case report provided an in-depth evaluation of occupational therapy combined with CCRT for early-onset AD in an effort to inform cognitive rehabilitation of patients with AD. ［Funded by Chengdu Medical Scientific Research Project （number， 2023635）］

Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.

AIM: To evaluate the efficacy of 0.05% cyclosporine eye drops in promoting ocular surface recovery following pterygium excision combined with autologous corneal limbal stem cell transplantation.METHODS:This study is a prospective randomized controlled trial, selecting 104 cases(104 eyes)of primary pterygium with monocular onset admitted to Baoding First Central Hospital from September 2023 to September 2024 as the initial sample. The patients were divided into an experimental group and a control group using a random number table method, with 52 eyes in each group. Both groups underwent pterygium excision and autologous corneal limbal stem cell transplantation performed by the same surgeon. The control group received tobramycin dexamethasone eye drops combined with 0.3% sodium hyaluronate eye drops, while the experimental group was additionally treated with 0.05% cyclosporine eye drops. The corneal epithelial repair status, ocular surface function [corneal fluorescein staining(FL)score, Schirmer I test(SIt), break-up time of tear film(BUT)] at preoperative and postoperative time points(1 and 3 mo), and dry eye symptoms [ocular surface disease index(OSDI), standard patient evaluation of eye dryness(SPEED)scores]. Additionally, the recurrence rate and postoperative complications were recorded.RESULTS: During the follow-up period, there was 1 case of loss to follow-up in both the experimental group and the control group, with lost to follow-up rate of 1.9%. Finally, 51 cases in each group completed all followed-up. No statistically significant difference was observed in preoperative general characteristics of patients between the two groups(P>0.05), and there was no statistically significant difference in corneal epithelial repair time or suture removal time(all P>0.05). At 1 mo postoperatively, the SIt and BUT decreased in both groups compared to preoperative levels, with the experimental group showing higher values than the control group(all P<0.05). FL scores increased compared to preoperative levels but were lower in the experimental group(all P<0.05). By 3 mo, the SIt, BUT and FL score of the control group were not statistically different from preoperative levels(all P>0.05), whereas the experimental group showed increased SIt and BUT, which were higher than the control group, and reduced FL scores, and decreased FL scores, which was lower than the control group(all P<0.05). At 3 mo postoperatively, both groups showed increased SIt and BUT compared to 1-month values, with the experimental group outperforming the control group(all P<0.05). FL scores decreased in both groups compared to 1-month values, with the experimental group maintaining lower scores(P<0.05). At 1 mo postoperatively, OSDI and SPEED scores were higher than preoperative levels, with the experimental group higher than the control group(all P<0.05); at 3 mo postoperatively, the scores returned to preoperative level(all P>0.05), and the OSDI and SPEED scores of the control group increased and higher than those of the experiment group(all P<0.05); at 3 mo postoperatively, the OSDI and SPEED scores decreased when compared with 1-month preoperative level, and the experiment group was lower than the control group(all P<0.05). There was no difference in the total incidence of postoperative complications between the two groups(P>0.05). According to the statistics of 6 mo follow-up after operation, there was no recurrence in the experimental group, and the recurrence rate was 11.8% in the control group(P<0.05).CONCLUSION: Adjunctive use of 0.05% cyclosporine eye drops after pterygium excision with limbal stem cell transplantation enhances ocular surface recovery, reduces dry eye symptoms, and lowers recurrence rates without compromising corneal epithelial healing or safety.

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

This study investigated the effect of Wuling San on transforming growth factor-β1(TGF-β1)-induced fibrosis, inflammation, and oxidative stress in human renal tubular epithelial cells(HK-2) and its mechanism of antioxidant stress injury. HK-2 cells were cultured in vitro and divided into a control group, a TGF-β1 model group, and three treatment groups receiving Wuling San-containing serum at low(2.5%), medium(5.0%), and high(10.0%) doses. TGF-β1 was used to establish the model in all groups except the control group. CCK-8 was used to analyze the effect of different concentrations of Wuling San on the activity of HK-2 cells with or without TGF-β1 stimulation. The expression of key fibrosis molecules, including actin alpha 2(Acta2), collagen type Ⅰ alpha 1 chain(Col1α1), collagen type Ⅲ alpha 1 chain(Col3α1), TIMP metallopeptidase inhibitor 1(Timp1), and fibronectin 1(Fn1), was detected using qPCR. The expression levels of inflammatory cytokines, including tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-4(IL-4), were measured using ELISA kits. Glutathione peroxidase(GSH-Px), malondialdehyde(MDA), catalase(CAT), and superoxide dismutase(SOD) biochemical kits were used to analyze the effect of Wuling San on TGF-β1-induced oxidative stress injury in HK-2 cells, and the expression of nuclear factor E2-related factor 2(Nrf2), heme oxygenase 1(HO-1), and NAD(P)H quinone oxidoreductase 1(NQO1) was analyzed by qPCR and immunofluorescence. The CCK-8 results indicated that the optimal administration concentrations of Wuling San were 2.5%, 5.0%, and 10.0%. Compared with the control group, the TGF-β1 model group showed significantly increased levels of key fibrosis molecules(Acta2, Col1α1, Col3α1, Timp1, and Fn1) and inflammatory cytokines(TNF-α, IL-1β, IL-6, IL-8, and IL-4). In contrast, the Wuling San administration groups were able to dose-dependently inhibit the expression levels of key fibrosis molecules and inflammatory cytokines compared with the TGF-β1 model group. Wuling San significantly increased the activities of GSH-Px, CAT, and SOD enzymes in TGF-β1-stimulated HK-2 cells and significantly inhibited the level of MDA. Furthermore, compared with the control group, the TGF-β1 model group exhibited a significant reduction in the expression of Nrf2, HO-1, and NQO1 genes and proteins. After Wuling San intervention, the expression of Nrf2, HO-1, and NQO1 genes and proteins was significantly increased. Correlation analysis showed that antioxidant stress enzymes(GSH-Px, CAT, and SOD) and Nrf2 signaling were significantly negatively correlated with key fibrosis molecules and inflammatory cytokines in the TGF-β1-stimulated HK-2 cell model. In conclusion, Wuling San can inhibit TGF-β1-induced fibrosis in HK-2 cells by activating the Nrf2 signaling pathway, improving oxidative stress injury, and reducing inflammation.
Humans ; Oxidative Stress/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Fibrosis/genetics* ; Cell Line ; Drugs, Chinese Herbal/pharmacology* ; Epithelial Cells/immunology* ; Inflammation/metabolism*