ObjectiveTo address the limitations of the current quality standard for Polygalae Radix（PR）， which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality， by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile， synchronous quantification of multiple index components， and quantitative analysis of multi-components by single marker（QAMS） for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography（HPLC） characteristic chromatograms were established for 11 batches of PR medicinal materials（YZ）， 10 batches of PR decoction pieces（YP）， and 10 batches of licorice-processed PR decoction pieces（ZYZ）， followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones（sibiricaxanthone B， polygalaxanthone Ⅺ， polygalaxanthone Ⅲ） in the characteristic chromatograms. Simultaneously， the external standard method（ESM） was used to determine the contents of the corresponding xanthones and 3，6'-disinapoyl sucrose in YZ， YP， and ZYZ， followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified， and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors（RCFs） of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88， and their relative retention times（RRTs） were 0.85 and 0.97， respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia）， the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP， as well as between YP and ZYZ， with 3，6'-disinapoyl sucrose identified as the main differentiating component. Furthermore， correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ， but showed no association with the content of 3，6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ，YP and ZYZ be revised to not less than 0.07%， or the total content of polygalaxanthone Ⅲ， sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms， precise quantification of oligosaccharide esters， and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.

BACKGROUND: Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported. METHODS: The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats. RESULTS: Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis. CONCLUSIONS A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Osteoarthritis, Knee/pathology* ; Chondrocytes/metabolism* ; Pyroptosis/physiology* ; HMGB1 Protein/genetics* ; MicroRNAs/metabolism* ; Endoplasmic Reticulum Stress/genetics* ; Humans ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Middle Aged

Objective To observe the correlations of chest CT quantitative parameters and one-year readmission in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods Totally 225 AECOPD patients were included and divided into the readmission group(group A,n=61)and non-readmission group(group B,n=164)according to whether readmitted due to acute exacerbation within one year or not.Quantitative CT parameters,including the percentage of low attenuation area volume to total lung volume(LAA％)and intrapulmonary vascular volume(IPVV)of the whole lung,left/right lung and each lobe,as well as the bronchial lumen area(LA)and percentage of bronchial wall area(WA％)of grades 3-8 were compared between groups.Spearman correlations were used to analyze the correlations between quantitative CT parameters and one-year readmission.Results LAA％of the whole lung,right lung,upper lobe of both lungs,middle lobe of the right lung,and lower lobe of the right lung in group A were higher than that in group B(all P＜0.05),which were weakly positively correlated with readmissions within one year(r=0.142-0.187,all P＜0.05).Significant differences of the upper lobe of right lung LAgrade 6,lower lobe of left lung LAgrade 6,lower lobe of left lung LAgrade 8,upper lobe of right lung WA％grade 5,upper lobe of right lung WA％grade 8 and lower lobe of left lung WA％grade 8 were found between groups,which were all correlated with readmissions within one year except for the lower lobe of the left lung LAgrade 6(all P＜0.05).Conclusion One-year readmission in AECOPD patients might be associated with severe airway remodeling and emphysema.

Objective : To investigate the therapeutic effects of a small interfering RNA(siRNA) vector targeting peptidyl arginine deaminase 4(PAD4) and splenocytes infected with a PAD4-siRNA virus, on collagen-induced arthritis(CIA) mice, and to elucidate the underlying mechanisms. Methods : The experiment mice were divided into four groups: control group, model group, therapy group 1 and therapy group 2, with 7 mice in each group. Control group mice were not treated. Initially, collagen-induced arthritis(CIA) mice model were established using bovine type II collagen. Model group mice were injected by PBS buffer Therapy group 1 mice were injected of PAD4-siRNA virus solution into the tail vein of the CIA mice, while therapy group 2 mice were injected of splenocytes infected with PAD4-siRNA virus via the same route. These injections were carried out once a week for a total of eight weeks. Subsequently, the alterations in T follicular helper(Tfh), T follicular regulatory(Tfr), T helper 1(Th1), and CD4+IL-10+T cells in the splenocytes of the mice were analyzed. Additionally, the pathological changes in the articular cartilage of the mice joints were detected. Results : Comparison with control group, mice of model group exhibited a significant increase in the proportions of Tfh and Th1 cells in the spleen(P<0.05), while the proportions of Tfr and CD4+IL-10+T cells remained unchanged. Comparison with model group, therapy group 1 and therapy group 2 demonstrated a significant decrease in the proportions of Tfh and Th1 cells(P<0.05), with no changes were observed in the proportions of Tfr and CD4+IL-10+T cells. Additionally, the articular surface in the mice of control group was smooth, whereas model group showed signs of inflammatory cell infiltration, rough articular surface, and cartilage destruction. Following treatment with PAD4-siRNA, the infiltration of inflammatory cells and cartilage destruction in the hind paws of CIA mice in therapy group 1 were reduced. However, no reduction was observed in the infiltration of inflammatory cells and cartilage destruction in the front paws of CIA mice. In contrast, therapy group 2 exhibited a reduction in the infiltration of inflammatory cells and cartilage destruction in both the front and hind paws of CIA mice. Conclusion Gene silencing of PAD4 expression can decrease the proportion of Tfh and Th1 cells, leading to an amelioration of pathological changes in joints and cartilage of hind paws. Furthermore, the therapeutic efficacy is observed in the front paws of CIA mice, and PAD4-siRNA plays a role on CIA mice by regulating T cells subpopulation of splenocytes.

Objective:To analyze the effect of joint management of type 2 diabetes mellitus (T2DM) between specialty and community under the model of National Diabetes Prevention and Control Center (DPCC).Methods:A total of 2 527 T2DM patients managed by DPCC Pingshan Center of Shenzhen from January 1, 2022 to December 31, 2024 were retrospectively included. After management, the rate of downturn, reexamination rate, blood pressure compliance rate, metabolic indicators (waist circumference, body mass index, fasting blood glucose, glycosylated hemoglobin, blood lipids) and screening rate of chronic complications of diabetes (atherosclerotic cardiovascular disease, microvascular disease, diabetic peripheral neuropathy) were analyzed. Those included 2022 ( n=564), 2023 ( n=1 477), and 2024 ( n=2 527). Results:The downturn rate in 2022, 2023 and 2024 increased year by year (22.8% vs 67.2% vs 89.9%, P<0.01), and the review rate (41.1% vs 62.2% vs 52.7%, P<0.01), complication screening rate (51.6% vs 85.3% vs 62.2%, P<0.01), blood pressure compliance rate (53.1% vs 78.0% vs 67.2%, P<0.01), body mass index compliance rate (13.2% vs 17.3% vs 28.6%, P<0.01), fasting blood glucose meeting rate (46.4% vs 60.2% vs 68.5%, P<0.01), glycated hemoglobin meeting rate (58.4% vs 63.2% vs 45.6%, P<0.01) were relatively improved. Waist circumference compliance rate (30.6% vs 27.7% vs 21.6%) and blood lipid compliance rate (33.6% vs 35.5% vs 31.9%) were not significantly improved, and the review rate, blood pressure compliance rate and complication screening rate in 2024 were lower than those in 2023 and higher than those in 2022. Conclusions:The combined management of type 2 diabetes under the DPCC model has significant effects on improving the down-conversion rate, rediagnosis rate, blood pressure compliance rate, metabolic index compliance rate and the screening rate of diabetes-related chronic complications in patients with diabetes. At the same time, it was also found that with the progress of hierarchical diagnosis and treatment, the review rate, complication screening rate, blood pressure, waist circumference, blood lipid and glycosylated hemoglobin reached the standard of patients decreased compared with the previous situation, which needs to be further analyzed and improved.

Objective:To analyze the effect of joint management of type 2 diabetes mellitus (T2DM) between specialty and community under the model of National Diabetes Prevention and Control Center (DPCC).Methods:A total of 2 527 T2DM patients managed by DPCC Pingshan Center of Shenzhen from January 1, 2022 to December 31, 2024 were retrospectively included. After management, the rate of downturn, reexamination rate, blood pressure compliance rate, metabolic indicators (waist circumference, body mass index, fasting blood glucose, glycosylated hemoglobin, blood lipids) and screening rate of chronic complications of diabetes (atherosclerotic cardiovascular disease, microvascular disease, diabetic peripheral neuropathy) were analyzed. Those included 2022 ( n=564), 2023 ( n=1 477), and 2024 ( n=2 527). Results:The downturn rate in 2022, 2023 and 2024 increased year by year (22.8% vs 67.2% vs 89.9%, P<0.01), and the review rate (41.1% vs 62.2% vs 52.7%, P<0.01), complication screening rate (51.6% vs 85.3% vs 62.2%, P<0.01), blood pressure compliance rate (53.1% vs 78.0% vs 67.2%, P<0.01), body mass index compliance rate (13.2% vs 17.3% vs 28.6%, P<0.01), fasting blood glucose meeting rate (46.4% vs 60.2% vs 68.5%, P<0.01), glycated hemoglobin meeting rate (58.4% vs 63.2% vs 45.6%, P<0.01) were relatively improved. Waist circumference compliance rate (30.6% vs 27.7% vs 21.6%) and blood lipid compliance rate (33.6% vs 35.5% vs 31.9%) were not significantly improved, and the review rate, blood pressure compliance rate and complication screening rate in 2024 were lower than those in 2023 and higher than those in 2022. Conclusions:The combined management of type 2 diabetes under the DPCC model has significant effects on improving the down-conversion rate, rediagnosis rate, blood pressure compliance rate, metabolic index compliance rate and the screening rate of diabetes-related chronic complications in patients with diabetes. At the same time, it was also found that with the progress of hierarchical diagnosis and treatment, the review rate, complication screening rate, blood pressure, waist circumference, blood lipid and glycosylated hemoglobin reached the standard of patients decreased compared with the previous situation, which needs to be further analyzed and improved.

Objective To observe the correlations of chest CT quantitative parameters and one-year readmission in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods Totally 225 AECOPD patients were included and divided into the readmission group(group A,n=61)and non-readmission group(group B,n=164)according to whether readmitted due to acute exacerbation within one year or not.Quantitative CT parameters,including the percentage of low attenuation area volume to total lung volume(LAA％)and intrapulmonary vascular volume(IPVV)of the whole lung,left/right lung and each lobe,as well as the bronchial lumen area(LA)and percentage of bronchial wall area(WA％)of grades 3-8 were compared between groups.Spearman correlations were used to analyze the correlations between quantitative CT parameters and one-year readmission.Results LAA％of the whole lung,right lung,upper lobe of both lungs,middle lobe of the right lung,and lower lobe of the right lung in group A were higher than that in group B(all P＜0.05),which were weakly positively correlated with readmissions within one year(r=0.142-0.187,all P＜0.05).Significant differences of the upper lobe of right lung LAgrade 6,lower lobe of left lung LAgrade 6,lower lobe of left lung LAgrade 8,upper lobe of right lung WA％grade 5,upper lobe of right lung WA％grade 8 and lower lobe of left lung WA％grade 8 were found between groups,which were all correlated with readmissions within one year except for the lower lobe of the left lung LAgrade 6(all P＜0.05).Conclusion One-year readmission in AECOPD patients might be associated with severe airway remodeling and emphysema.

Objective:To build a nursing care plan decision-making support system based on the hospital's nursing information system and evaluate its effects in newly hired nurses.Methods:This study adopted a non-synchronous pre-post control design. Totally 181 newly hired nurses recruited by Beijing Tiantan Hospital, Capital Medical University, were selected by convenience sampling. The control group consisted of 85 new nurses hired in August 2021, while the intervention group consisted of 96 new nurses hired in August 2022. The control group received traditional training methods, while the intervention group received training through the nursing care plan decision-making support system in addition to the traditional methods. The nursing decision-making ability and the quality of specialty nursing care were compared between the two groups.Results:Finally, 81 nurses were included in the control group, and 93 nurses were included in the intervention group. The nursing decision-making ability score in the intervention group was (80.15±4.59), which was significantly higher than the (78.62±5.13) in the control group ( t=-2.080, P=0.039). The intervention group also had a significantly higher qualified rate of specialty nursing care compared to the control group (χ 2=6.626, P=0.036) . Conclusions:The application of the nursing care plan decision-making support system in the standardized training of newly hired nurses can improve their nursing decision-making abilities and the quality of specialty nursing care.

Objective To observe the correlations of chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with blood eosinophil(EOS)level.Methods Chest CT data of 162 AECOPD patients with elevated eosinophils were retrospectively analyzed.The patients were divided into low EOS group(n=105)and high EOS group(n=57)according to the absolute counting of blood EOS.The quantitative CT parameters,including the number of whole lung bronchi and the volume of blood vessels,low-attenuation area percentage(LAA％)of whole lung,of left/right lung and each lobe of lung,as well as the luminal diameter(LD),wall thickness(WT),wall area(WA)and WA percentage of total bronchial cross-section(WA％)of grade 3 to 8 bronchi were compared between groups.Spearman correlations were performed to analyze the correlations of quantitative CT parameters with blood EOS level.Results LAA％of the whole lung,of the left/right lung and each lobe of lung,as well as of the upper lobe of right lung LDgrade4,middle lobe of right lung WTgrade5,upper lobe of right lung WAgrade4,middle lobe of right lung WAgrade5 and lower lobe of left lung WAgrade3 in low EOS group were all higher than those in high EOS group(all P＜0.05).Except for the upper lobe of right lung LDgrade4,the above quantitative CT indexes being significant different between groups were all weakly and negatively correlated with blood EOS level(r=-0.335 to-0.164,all P＜0.05).Conclusion Chest CT quantitative parameters of AECOPD patients were correlated with blood EOS level,among which LAA％,a part of WT and WA were all weakly negatively correlated with blood EOS level.

Objective:To investigate the therapeutic effects of a small interfering RNA (siRNA) targeting hypoxia inducible factor-1α (HIF-1α) on collagen-induced arthritis (CIA) in mice and to analyze the possible mechanism at the macrophage level.Methods:DBA/1 mice were injected with bovine type Ⅱ collagen to establish the CIA model. Then, they were injected with HIF-1α-siRNA adenovirus or negative control adenovirus through tail vein once a week for four weeks. This study included four groups: control group, CIA model group, negative control group and HIF-1α-siRNA group. Mouse bone marrow-derived macrophages (BMDMs) were isolated and cultured. The relative expression of CD206 and arginine (Arg) at mRNA level in mouse BMDMs was detected by RT-PCR. The proportions of F4/80 + CD16/32 + M1 and F4/80 + CD206 + M2 macrophages in spleen and thymus were detected by flow cytometry. Pathological changes in the ankle joint of mice were observed using HE staining. Immunohistochemistry was used to detect the expression of macrophages and the subsets in mouse synovial tissues. Results:(1) Compared with the control group, the CIA model group showed decreased expression of CD206 at mRNA level in BMDMs, but increased expression of Arg at mRNA level ( P<0.01). HIF-1α-siRNA increased the expression of CD206 at mRNA level ( P<0.05) and reduced the expression of Arg at mRNA level in BMDMs of mice with CIA ( P<0.01). (2) Compared with the control group, the mice in the CIA model group had increased proportions of F4/80 + CD16/32 + M1 macrophages in splenocytes and thymocytes ( P<0.05), but decreased proportions of F4/80 + CD206 + M2 macrophages in thymocytes ( P<0.05). HIF-1α-siRNA could down-regulate the proportions of F4/80 + CD16/32 + M1 macrophages in splenocytes and thymocytes ( P<0.05), and up-regulate the proportions of F4/80 + CD206 + M2 macrophages in thymocytes of CIA mice ( P<0.01). (3) CIA mice had synovial hyperplasia and macrophages infiltration, especially M1 macrophages, in the ankle joint. HIF-1α-siRNA could alleviate the synovial hyperplasia and macrophage infiltration. Conclusions:HIF-1α-siRNA could alleviate macrophage infiltration and synovial hyperplasia in CIA mice through reducing the proportions of M1 macrophages in thymocytes, BMDMs and synovial tissues and increasing the proportion of M2 macrophages, suggesting that HIF-1α-siRNA could treat CIA mice by regulating the differentiation of M1 and M2 macrophages.