ObjectiveThis paper aims to conduct the feature analysis and correlation analysis on the ocular collateral features and differential metabolites in patients with chronic hepatitis B （CHB） complicated by glucose metabolism disorder （GMD），particularly those with the damp-heat syndrome type，by integrating shadowless scleral imaging and metabolomics technologies. MethodsA total of 313 patients were recruited from the Hepatology and Endocrinology Outpatient Departments of Public Health Clinical Center of Chengdu according to the inclusion/exclusion criteria，and they were divided into a CHB group and a CHB complicated by GMD groups （damp-heat syndrome group and non-damp-heat syndrome group）. All patients underwent high-definition ocular image acquisition and feature extraction using an intelligent analysis system for shadowless scleral imaging to analyze the differences in the counting of morphological feature scores of ocular collaterals among groups. By using a digital sampling method，24 patients from each group were randomly selected，along with 20 healthy volunteers，for untargeted metabolomic analysis of peripheral serum. Differential metabolites were identified，statistically analyzed，and subjected to potential biomarker analysis and pathway enrichment. Spearman method was performed to conduct the correlation analysis on the differential ocular collateral features and differential metabolites，followed by correlation network construction. ResultsCompared with those in the CHB group，patients with CHB complicated by GMD showed significant changes in ocular collateral feature scores such as "hillock"，"blood vessels"，and "pale dusky coloration" （P<0.05）. In comparison with those in the healthy group，metabolites including N-acetylglucosamine，acetylhomoserine，and myo-inositol （AUC>0.7） were identified as potential biomarkers for the disease. Compared with those in the CHB complicated by GMD group with non-damp-heat syndrome，patients with damp-heat syndrome exhibited significant changes in feature scores of "plaques"，"yellow coloration"，"spleen"，and "gallbladder" （P<0.05）. In comparison with those in the healthy group，metabolites such as O²′-4a-cyclic tetrahydrobiopterin，theobromine，xanthurenic acid，and L-glutamic acid 5-phosphate （AUC>0.7） were identified as potential biomarkers for the damp-heat syndrome type. The Spearman correlation analysis reveals weak to moderate linear correlations between the differential scleral collateral features and metabolites. By constructing a "disease-syndrome" network of ocular diagnosis and metabolites，"xanthurenic acid-gallbladder" and "theobromine-plaque/yellow coloration" were identified as specific molecular-phenotypic correlated biomarker clusters for CHB complicated by GMD with dampness-heat syndrome. ConclusionPatients with CHB complicated by GMD demonstrate differential ocular diagnostic features and serum metabolites corresponding to disease states and dampness-heat syndrome. These objective biomarkers can guide both clinical syndrome differentiation and medication. The macro-micro integration based on ocular feature clusters and potential metabolic biomarkers offers an innovative approach to a combined traditional Chinese and Western medicine diagnosis and treatment model for this disease.

Objective:To study the expression of serum microRNA (miRNA)-335 and miRNA-375 in patients with papillary thyroid carcinoma (PTC) and their relationship with pathological features and prognosis.Methods:Using a case-control study method, 94 PTC patients admitted to Huaian Hospital of Huaian City from March 2021 to March 2023 were selected as PTC group. Another 73 healthy individuals who underwent physical examinations during the same period were selected as control group. Quantitative real-time PCR was used to determine the relative expression levels of serum miRNA-335 and miRNA-375. PTC patients were followed up until September 30, 2024, and the patient's prognosis was record. The relative expression levels of serum miRNA-335 and miRNA-375 were compared between the two groups, among different pathological features, and among patients with different prognoses. Multivariate logistic regression analysis was performed to identify independent risk factors for prognosis in PTC patients.Results:The relative expression level of serum miRNA-335 in the PTC group (2.35 ± 0.68) was higher than that in the control group (0.98 ± 0.04), while the relative expression level of miRNA-375 (0.65 ± 0.21) was lower than that in the control group (1.01 ± 0.02, P < 0.001). There was no statistically significant differences in the relative expression levels of serum miRNA-335 and miRNA-375 among PTC patients with different tumor diameters, tumor locations, tumor numbers, and vascular invasion ( P > 0.05). The relative expression level of serum miRNA-335 in TNM stages Ⅲ - Ⅳ was higher than that in stages Ⅰ - Ⅱ, while the relative expression level of miRNA-375 in TNM stages Ⅲ - Ⅳ was lower than that in stages Ⅰ - Ⅱ ( P < 0.001). The relative expression level of serum miRNA-335 of patients with lymph node metastasis was higher than that of patients without lymph node metastasis, while the relative expression level of serum miRNA-375 of patients with lymph node metastasis was lower than that of patients without lymph node metastasis ( P < 0.001). The relative expression level of serum miRNA-335 in the poor prognosis group was higher than that in the good prognosis group, while the relative expression level of miRNA-375 in the poor prognosis group was lower than that in the good prognosis group ( P < 0.001). Vascular invasion, lymph node metastasis, high expression of miRNA-335, and low expression of miRNA-375 were all independent risk factors for prognosis in PTC patients ( P < 0.05). Conclusion:Patients with PTC have high serum miRNA-335 expression and low miRNA-375 expression, and the expression of miRNA-335 and miRNA-375 is closely related to TNM staging, lymph node metastasis, and prognosis, which deserves clinical attention.

AIM To study the chemical constituents from the stems and leaves of Dendrobium formosum Roxb.ex Lindl.and their biological activities.METHODS The 95％ethanol extract from the stems and leaves of D.formosum was isolated and purified by silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their inhibitory activities onα-glucosidase were determined by PNPG method,and their in vitro anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Fifteen compounds were isolated and identified as coniferyl p-coumarate(1),(-)-pinoresinol(2),2,5,7-trihydroxy-4-methoxy-9,10-dihydrophenanthrene(3),naringenin(4),spiropreussomerin A(5),7-hydroxy-14-de-O-methyl-lasiodiplodin(6),(4S,5S,6Z,8E)-5-hydroxydeca-6,8-dien-4-olide(7),(6S,9R)-blumenol C(8),p-hydroxybenzoic acid(9),m-hydroxybenzoic acid(10),p-hydroxy benzenepropanoic acid(11),5,7-dihydroxy-isobenzofuran(12),2-(4-hydroxyphenyl)-ethanol(13),β-sitostenone(14),β-sitosterol(15).The IC50 values of compounds 1 and 4 on α-glucosidase inhibition were(65.60±3.31)and(98.95±2.53)μmol/L,respectively.Compound 3 presented inhibitory activity on NO production in RAW 264.7 cells,with IC50 value of(3.97±0.12)μmol/L.CONCLUSION Compounds 5-6,8 and 12 are isolated from Orchidacae family for the first time,and 2-15 are first isolated from this plant.Compounds 1 and 4 have α-glucosidase inhibitory activities,and 3 has anti-inflammatory activity.

AIM To study the chemical constituents from the stems and leaves of Dendrobium formosum Roxb.ex Lindl.and their biological activities.METHODS The 95％ethanol extract from the stems and leaves of D.formosum was isolated and purified by silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their inhibitory activities onα-glucosidase were determined by PNPG method,and their in vitro anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Fifteen compounds were isolated and identified as coniferyl p-coumarate(1),(-)-pinoresinol(2),2,5,7-trihydroxy-4-methoxy-9,10-dihydrophenanthrene(3),naringenin(4),spiropreussomerin A(5),7-hydroxy-14-de-O-methyl-lasiodiplodin(6),(4S,5S,6Z,8E)-5-hydroxydeca-6,8-dien-4-olide(7),(6S,9R)-blumenol C(8),p-hydroxybenzoic acid(9),m-hydroxybenzoic acid(10),p-hydroxy benzenepropanoic acid(11),5,7-dihydroxy-isobenzofuran(12),2-(4-hydroxyphenyl)-ethanol(13),β-sitostenone(14),β-sitosterol(15).The IC50 values of compounds 1 and 4 on α-glucosidase inhibition were(65.60±3.31)and(98.95±2.53)μmol/L,respectively.Compound 3 presented inhibitory activity on NO production in RAW 264.7 cells,with IC50 value of(3.97±0.12)μmol/L.CONCLUSION Compounds 5-6,8 and 12 are isolated from Orchidacae family for the first time,and 2-15 are first isolated from this plant.Compounds 1 and 4 have α-glucosidase inhibitory activities,and 3 has anti-inflammatory activity.

Background: We investigated osteoporosis management strategies and clinical outcomes following the occurrence of medicationrelated osteonecrosis of the jaw (MRONJ). Methods: We retrospectively studied individuals diagnosed with MRONJ during osteoporosis treatment who were managed in the Osteoporosis Center or the Oral Maxillofacial Surgery & Dental Unit at Queen Mary Hospital in Hong Kong between 2010 and 2022. We examined subsequent osteoporosis management plans, fracture events, and bone mineral density (BMD). Results: Thirty-six individuals were included (mean age, 78.5 years; 94.4% women). The estimated prevalence of MRONJ was 0.26%. All patients had been exposed to bisphosphonates, and seven had also received denosumab before MRONJ. Following MRONJ, only 14 individuals continued anti-osteoporosis treatment, a decision influenced by a higher fracture probability at MRONJ onset. The most common regimen was a teriparatide-raloxifene sequence (n=8): three patients achieved stable BMD, four achieved improving BMD, and one exhibited a mixed response. The patient with a mixed BMD response had also been treated with denosumab. Six patients sustained incident fractures after MRONJ, and these patients had lower BMD T-scores than their counterparts. Two patients experienced MRONJ recurrence, which was associated with the resumption of bisphosphonate or denosumab therapy after MRONJ. These patients had higher BMD T-scores than those who did not experience MRONJ recurrence. Conclusion MRONJ is challenging because high fracture risk necessitates discontinuation of antiresorptive agents. Teriparatide followed by raloxifene may be a reasonable regimen. Individualised decisions in osteoporosis management after MRONJ are required to balance fracture risk reduction with minimising MRONJ recurrence.

Objective:To study the expression of serum microRNA (miRNA)-335 and miRNA-375 in patients with papillary thyroid carcinoma (PTC) and their relationship with pathological features and prognosis.Methods:Using a case-control study method, 94 PTC patients admitted to Huaian Hospital of Huaian City from March 2021 to March 2023 were selected as PTC group. Another 73 healthy individuals who underwent physical examinations during the same period were selected as control group. Quantitative real-time PCR was used to determine the relative expression levels of serum miRNA-335 and miRNA-375. PTC patients were followed up until September 30, 2024, and the patient's prognosis was record. The relative expression levels of serum miRNA-335 and miRNA-375 were compared between the two groups, among different pathological features, and among patients with different prognoses. Multivariate logistic regression analysis was performed to identify independent risk factors for prognosis in PTC patients.Results:The relative expression level of serum miRNA-335 in the PTC group (2.35 ± 0.68) was higher than that in the control group (0.98 ± 0.04), while the relative expression level of miRNA-375 (0.65 ± 0.21) was lower than that in the control group (1.01 ± 0.02, P < 0.001). There was no statistically significant differences in the relative expression levels of serum miRNA-335 and miRNA-375 among PTC patients with different tumor diameters, tumor locations, tumor numbers, and vascular invasion ( P > 0.05). The relative expression level of serum miRNA-335 in TNM stages Ⅲ - Ⅳ was higher than that in stages Ⅰ - Ⅱ, while the relative expression level of miRNA-375 in TNM stages Ⅲ - Ⅳ was lower than that in stages Ⅰ - Ⅱ ( P < 0.001). The relative expression level of serum miRNA-335 of patients with lymph node metastasis was higher than that of patients without lymph node metastasis, while the relative expression level of serum miRNA-375 of patients with lymph node metastasis was lower than that of patients without lymph node metastasis ( P < 0.001). The relative expression level of serum miRNA-335 in the poor prognosis group was higher than that in the good prognosis group, while the relative expression level of miRNA-375 in the poor prognosis group was lower than that in the good prognosis group ( P < 0.001). Vascular invasion, lymph node metastasis, high expression of miRNA-335, and low expression of miRNA-375 were all independent risk factors for prognosis in PTC patients ( P < 0.05). Conclusion:Patients with PTC have high serum miRNA-335 expression and low miRNA-375 expression, and the expression of miRNA-335 and miRNA-375 is closely related to TNM staging, lymph node metastasis, and prognosis, which deserves clinical attention.

Background: We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19. Methods: COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes. Results: Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m2 to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group. Conclusion Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demon-strated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel anti-angiogenic therapy for endometriosis.

Objective To study the effect of Qingke Pingchuan Granule on the clinical efficacy in patients with phlegm-heat obstructing lung syndrome(AECOPD).Methods A total of 80 patients with acute exacerbation of chronic obstructive pulmonary disease(syndrome of phlegm-heat stagnation in the lung)hospitalized in the respiratory department of our hospital were selected and divided into the conventional group and the combinational group,with 40 cases in each group.The CAT score,TCM syndrome score,serum IL-6,CRP,lung function FEV1%pred,and FEV1/FVC were retrospectively observed before treatment,at the end of the second week of treatment,and at the follow-up after 1 month of treatment in the two groups.Results The total effective rate was significantly better in the combinational group than that of the conventional group(92.5%vs.75.0%,P＜0.05).At the end of the second week of treatment,the CAT score,each single syndrome score,serum IL-6 and CRP levels were all improved than those before treatment in the two groups(P＜0.05),and the improvement degree was better in the combined group than that of the conventional group(P＜0.05).The severity of airflow limitation and respiratory failure were significantly improved compared with those before treatment in both groups.At the follow-up after 1 month of treatment,the recovery rate of scores of each single syndrome score and CAT score were significantly lower in the combined group than those in the routine group(P＜0.05).There were no significant differences in adverse drug reactions between the two groups(12.5%and 2.5%,P＞0.05).Conclusion Qingke Pingchuan Granule can effectively relieve the symptoms and improve lung function and the quality of life of AECOPD patients.

[Abstract] Objective To establish an inflammation model by stimulating BV2 microglia by lipopolysaccharide, and to explore the regulation effect of ginsenoside Rg1 on inflammation by activating peroxisome proliferator activated receptor γ(PPARγ) receptor protein. Methods BV2 microglia were randomly divided into control group, model group, ginsenoside Rg1 group, rosiglitazone group and GW9662 group. The control group did not do any treatment, the model group was treated with 1 mg/ L lipopolysaccharide, and the other groups were treated with lipopolysaccharide added with 0. 4 mmol/ L ginsenoside Rg1, 10 μmol/ L rosiglitazone or 10 μmol/ L respectively. GW9662. The proliferation of BV2 microglia in each group was detected by CCK-8 method; PPAR-γ, phospho-NF-κB p65 (p-NF-κB p65), induced expression of inducible nitric oxide synthase(iNOS) and human arginase 1(ARG-1) proteins. ELISA was used to detect the inflammatory factors interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-8(IL-8) and the content of tumor necrosis factor-α (TNF-α). Results Compared with the control group, the cell proliferation rate in the model group was significantly increased, and the contents of IL-1β, IL-6, IL-8 and TNF-α increased significantly. The result of immunofluorescence and Western blotting showed that iNOS and p-NF-κB p65 increased significantly, and the positive expressions of PPARγ and ARG-1 decreased significantly(both P<0. 01). The expression level of TNF-α decreased, the positive expressions of iNOS and p-NF-κB p65 decreased significantly, and the positive expressions of PPARγ and ARG-1 increased significantly(all P<0. 01). Conclusion Ginsenoside Rg1 inhibits the inflammatory response of BV2 microglia after lipopolysaccharide stimulation, and its mechanism may be related to the regulation of PPARγ/ NF-κB pathway to promote the M2-type polarization of microglia.