ObjectiveTo explore the effect and mechanism of Qigui Didang decoction， formulated based on the principle of Tonifying Deficiency and Unblocking Collaterals， on improving metabolic memory of db/db mice with diabetic nephropathy （DN） through silent information regulator 1 signal regulator 1 （Sirt1）/p53/nuclear factor kappa-B （NF-κB） p65 pathway. MethodsFifteen db/db mice were randomly divided into model group （10 mL·kg^-1·d^-1）， resveratrol group （20 mg·kg^-1·d^-1）， and Qigui Didang decoction group （3.34 g·kg^-1·d^-1） Another five db/m mice were selected as the normal group （10 mL·kg^-1·d^-1）. After the intervention， the kidney weight of each group was measured， and the kidney index （KI） was calculated. Fasting blood glucose （FBG）， creatinine （CRE）， β2-microglobulin （β2-MG）， blood urea nitrogen （BUN）， and cystatin C （CysC） were measured. Renal pathology was observed by hematoxylin-eosin （HE） staining and Masson staining. The mRNA and protein expression levels of Sirt1， NF-κB， tumor suppressor gene p53， interleukin-1β （IL-1β）， and cysteine aspartate protease-3 （Caspase-3） were detected using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultsCompared with the normal group， the model group showed disordered renal structure， obvious renal damage， and markedly elevated levels of renal function indexes （CRE， β2-MG， BUN， and CysC） （P<0.01）. The KI and blood glucose were significantly increased （P<0.01）， while Sirt1 expression was markedly decreased （P<0.01）. Expression levels of NF-κB p65， p53， IL-1β， and Caspase-3 were increased significantly （P<0.05）. Compared with those in the model group， DN mice treated with Qigui Didang decoction exhibited significantly decreased FBG， improved renal function， and markedly decreased KI （P<0.01）， along with reduced CRE， β2-MG， BUN， and CysC levels （P<0.05）. Protein expression of Sirt1 was significantly upregulated （P<0.05）， while that of NF-κB p65， p53， IL-1β， and Caspase-3 was markedly decreased （P<0.05）. The mRNA expression levels of NF-κB p65， p53， IL-1β， and Caspase-3 were significantly decreased （P<0.05）. The staining results indicate improved renal fibrosis， significantly decreased fiber deposition （P<0.05）， and less inflammatory infiltration in the Qigui Didang decoction group. ConclusionThe findings suggest that Qigui Didang decoction can alleviate the metabolic memory effect of DN， thereby inhibiting renal cell apoptosis and inflammatory response in mice， and improving renal function. The mechanism of action is closely related to the Sirt1/p53/NF-κB p65 signaling pathway.

BackgroundPrevious studies have identified a close relationship among psychological neglect and abuse， negative affect， different stages of adolescence， and suicidal ideation. However， the mechanisms underlying the impact of psychological abuse and neglect on suicidal ideation among left-behind adolescents remain unclear， and this field of research is still in its relative infancy. ObjectiveTo explore the relationship between psychological neglect/abuse and suicidal ideation among left-behind adolescents， as well as the mediating role of negative affect and the moderating effect of different stages of adolescence， so as to provide insights for preventing and intervening suicidal ideation in this population. MethodsFrom November 2021 to May 2022， a cluster random sampling technique was utilized to select 2 309 left-behind adolescents in western China. Assessments were conducted using the Child Psychological Abuse and Neglect Scale （CPANS）， the Positive and Negative Suicide Ideation （PANSI） and the Positive and Negative Affect Schedule for Children （PANAS-C）. Spearman correlation coefficients were calculated across all samples， and Process 4.1 was employed to test the mediating role of negative affect and the moderating role of different stages of adolescence in the pathway linking psychological abuse/neglect to suicidal ideation. ResultsA total of 2 119 left-behind adolescents （mean age： 14.94±1.20 years） completed the study， with males comprising 51.34% （1 088/2 119） and females 48.66% （1 031/2 119）.Among left-behind adolescents， scores on CPANS psychological neglect subscale showed positive correlations with both psychological abuse subscale scores and PANAS-C negative affect subscale scores （r=0.446， 0.496， P<0.01）. Additionally， CPANS psychological neglect and psychological abuse subscale scores were also positively correlated with PANSI scores （r=0.487， 0.508， P<0.01）. Furthermore， PANAS-C negative affect subscale scores demonstrated a positive correlation with PANSI scores （r=0.499， P<0.01）. Negative affect partially mediated the relationship between psychological abuse/psychological neglect and suicidal ideation， with effect sizes of 0.166 （95% CI： 0.141~0.191） and 0.131 （95% CI： 0.112~0.152）. Different stages of adolescence moderated the latter part （negative emotion → suicidal ideation） of the indirect mediation path from psychological neglect to suicidal ideation through negative affect （β=-0.066， P<0.01）. ConclusionBoth psychological neglect and psychological abuse may influence suicidal ideation among left-behind adolescents via negative affect. Moreover， different stages of adolescence may moderate the indirect path from psychological neglect to suicide ideation through negative affect.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective:To compare the therapeutic effects of different inhaled medications on patients with frequent cough in chronic obstructive pulmonary disease (COPD), including changes in symptoms and acute exacerbation.Methods:This study was based on the RealDTC study, and the study subjects were stable COPD patients from the Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital, Central South University from December 2016 to March 2023. The demographic characteristics, smoking status, history of biofuel exposure, history of acute exacerbation in the past year, lung function, COPD Assessment Test (CAT) score, modified British Medical Research Council Respiratory Difficulty Questionnaire (mMRC) score, and inhalation medication regimen of the patients were collected. Patients with frequent cough are defined as having a cough score of ≥2 in the first item of the CAT score. According to the type of inhaled medication, patients with frequent cough are divided into l long-acting muscarine anticholinergic (LAMA), long-acting β2 agonists (LABA)+ LAMA, inhaled corticosteroids (ICS)+ LABA, and ICS+ LABA+ LAMA groups. At the 6th month follow-up, CAT scores were collected and symptom control was evaluated, including minimum clinical improvement (MCID) (defined as a decrease of ≥2 points from baseline in CAT scores at the 6th month) and improvement in cough symptoms (defined as a decrease of ≥1 point from baseline in cough scores). During a one-year follow-up, the number of acute exacerbations was evaluated. The relationship between different inhaled medications and prognosis in patients with frequent cough in COPD was evaluated using multivariate logistic regression analysis.Results:A total of 653 patients with frequent cough in COPD were included, with a CAT score of (16.4±6.1) and a cough score of 3(2, 3). After 6 months of follow-up, 403 patients (61.7%) achieved MCID, and 394 patients (60.3%) had improved cough symptoms; During a one-year follow-up, 227 patients (34.8%) experienced acute exacerbation. After receiving inhalation medication treatment, the CAT scores and cough scores of four groups of patients with frequent cough, namely LAMA, LABA+ LAMA, ICS+ LABA, and ICS+ LABA+ LAMA, decreased compared to before treatment (all P<0.05). There was a statistically significant difference in the proportion of △CAT score, MCID, and acute exacerbation among the four groups of LAMA, LABA+ LAMA, ICS+ LABA, and ICS+ LABA+ LAMA (all P<0.05), while there was no statistically significant difference in the proportion of △cough score and cough score reduction ≥1 point (all P>0.05). The results of multivariate logistic regression analysis showed that compared with patients treated with LAMA or ICS+ LABA drugs, patients with frequent cough in COPD treated with LABA+ LAMA or ICS+ LABA+ LAMA drugs were more likely to achieve MCID and less likely to experience acute exacerbation (all P<0.05). Conclusions:Compared with LAMA or ICS+ LABA, patients with frequent cough in COPD who receive LABA+ LAMA or ICS+ LABA+ LAMA drug treatment are more likely to improve symptoms and have a lower risk of acute exacerbation.

Objective:To explore the impact of sleep disorders on the therapeutic effects of different inhaled medications in patients with chronic obstructive pulmonary disease (COPD).Methods:A prospective observational study was conducted on 393 patients with stable COPD who visited the Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University from December 2020 to September 2021. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of patients with chronic obstructive pulmonary disease, and patients were divided into a non sleep disorder group and a sleep disorder group. The Berlin questionnaire was used to assess the risk of obstructive sleep apnea syndrome (OSAS) in patients, and the hospital anxiety and depression questionnaire (HADS) was used to assess the presence of anxiety and depression in patients. The improvement of symptoms [minimum clinically significant difference (MCID)] and the deterioration of symptoms [clinical significant symptom deterioration (CID)] within six months of patient follow-up were evaluated. The moderate to severe acute exacerbation of the patient was recorded during the one-year follow-up period. The clinical characteristics of two groups of patients were compared, and multiple regression analysis was used to evaluate the relationship between sleep quality and the prognosis of chronic obstructive pulmonary disease, as well as the impact of sleep disorders on the treatment efficacy of different inhaled drugs.Results:The average age of 393 patients with chronic obstructive pulmonary disease was (62.9±8.3)years old, with a median percentage of forced expiratory volume in the first second (FEV 1%) of 53.7%(30.7%) and a mean PSQI score of (5.7±3.4)points. 186 cases (47.3%) of patients had sleep disorders. Compared with patients in the non sleep disorder group, patients in the sleep disorder group had a higher proportion of middle school education and below, lower FEV 1 and FEV 1/forced vital capacity (FVC), higher baseline COPD Assessment Test (CAT), modified Medical Research Council (mMRC) and Clinical COPD Questionnaire (CCQ) scores, and a higher proportion of comorbid anxiety (all P<0.05). Compared with patients without sleep disorders, patients with sleep disorders had a lower incidence of MCID ( P=0.030) and a higher incidence of CID ( P=0.005). During the one-year follow-up period, patients with sleep disorders experienced a higher proportion of moderate to severe acute exacerbation ( P=0.001), severe acute exacerbation ( P=0.003), and frequent acute exacerbation ( P=0.009). The results of multiple regression analysis showed that patients with sleep disorders had a lower likelihood of developing MCID ( OR: 0.288, 95% CI: 0.145-0.379, P<0.001), and an increased risk of developing CID ( OR: 3.150, 95% CI: 2.011-4.388, P<0.001) and acute exacerbation ( OR: 1.659, 95% CI: 1.162-2.368, P=0.005). Compared with patients using long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS)+ long-acting β2-agonist (LABA), patients in the sleep disorder group who used LABA+ LABA were more likely to develop MCID ( OR: 1.420, 95% CI: 1.021-2.751, P=0.010; OR: 1.976, 95% CI: 1.123-2.227, P=0.023). Conclusions:Compared with patients without sleep disorders, COPD patients with sleep disorders have a lower likelihood of symptom improvement, and a higher risk of symptom deterioration and acute exacerbation.Patients with COPD with sleep disorders are more likely to achieve symptom improvement by using LABA+ LAMA.

Objective:To investigate the clinical value of electronic laryngoscope combined with narrow band imaging（NBI） endoscope and its classification in the diagnosis of vocal cord leukoplakia. Methods:A retrospective analysis was performed on 115 cases of patients treated in the Department of Otolaryngology, Head and Neck Surgery, Nanjing Drum Tower Hospital from September 2020 to November 2022. All 115 cases were diagnosed with vocal cord leukogramma using the electronic laryngoscopy and narrow band imaging endoscopy, followed by pathological examination in the outpatient tissue biopsy. The morphological characteristics of vocal cord leukoplakia and the correlation between narrow band imaging classification and pathological results were investigated. Results:Among 115 cases of vocal cord leukoplakia, 46 cases（40.00%） were diagnosed as benign lesions. Low grade intraepithelial neoplasia occurred in 29 cases（25.22%）. High-grade intraepithelial neoplasia（including carcinoma in situ） occurred in 22 cases（19.13%）. Invasive carcinoma（including suspected invasive carcinoma） was found in 18 cases（15.65%）. There were no statistical differences in the unilateral and bilateral distribution of vocal cord leukoplakia and pathological results（P>0.05）, but there were statistical differences in the size, thickness, lesion uniformity, clear boundary, pre-invasion commissure, symmetry,age over 55 years old, morphological classification, NBI classification and pathological results distribution（P<0.05）. The two-by-two comparison among the three groups of morphological classification（flat type, raised type, rough type） showed that P<0.017 was only compared between flat type and rough type, and P>0.017 was compared between the other two groups. The pairwise comparison among the three groups of NBI classification（Ⅲ, Ⅳ, Ⅴ） was statistically significant（P<0.017）. There was a high correlation between NBI classification and pathological diagnosis, and the correlation coefficient was 0.705（P<0.05）. The risk of high intraepithelial neoplasia and cancerization in type Ⅳ was 9.125 times higher than that in type Ⅲ, and the risk of high intraepithelial neoplasia and cancerization in type Ⅴ was 271.078 times higher than that in type Ⅲ. The area under the curve of morphological classification and NBI classification were 0.672 and 0.896, respectively. Conclusion:There is a high match and correlation between NBI classification and pathological diagnosis. Electronic laryngoscope combined with narrow band imaging endoscope has a high diagnostic value for vocal cord leukoplakia, and a strong predictive ability for malignant leukoplakia.
Humans ; Vocal Cords/pathology* ; Male ; Female ; Leukoplakia/diagnosis* ; Narrow Band Imaging/methods* ; Retrospective Studies ; Laryngoscopy/methods* ; Middle Aged ; Laryngeal Neoplasms/diagnosis* ; Aged ; Laryngoscopes ; Adult

Objective:Considering the large amount and poor quality of clinical data, this study aims to explore the establishment of high-quality research database and its role in real-world research by taking the establishment of lymphoma research database as an example.Methods:The expert opinions in the field of lymphoma were collected, and the relevant guidelines and standards were referenced to establish a standard medical knowledge dataset. The electronic diagnosis and treatment data of lymphoma patients treated in Peking University Cancer Hospital from February 2005 to December 2020 were retrospectively extracted, the deep Learning, natural language processing were adopted to build a dynamic intelligent information integration and processing system of " lymphoma database based on electronic medical record system - biological sample information database - extended genetic information database" .Results:The research database not only meets the research needs of clinical researchers, but also realizes the management of traces in the whole process of application, approval, traceability and analysis of hospital medical record data and biological sample data. The total number of research variables in the database was 668, and the structured variables accounted for 46.0%. On December 25, 2021, there were 68 687 lymphoma patients in the database, the ratio of male to female patients was 8/9, and the proportion of patients with ≥3 visits accounted for 23.0%. In addition, researchers can superimpose searches in the database according to the target conditions, display the targeted medical records according to research hypothesis, and then establish a research cohort, conducting statistical modeling, and mining data information.Conclusions:By integrating management processes and using new natural language artificial intelligence technology to establish a high-level evidence-based database, it is helpful for the interconnection and resource sharing of hospital information systems, so as to achieve the purpose of providing reliable and detailed data for real-world research.

Periodontitis is a complex chronic inflammatory disease. The invasion of pathogens induces the inflammatory microenvironment in periodontitis. Cell behavior changes in response to changes in the microenvironment, which in turn alters the local inflammatory microenvironment of the periodontium through factors secreted by cells. It has been confirmed that periodontal ligament stem cells (PDLSCs) are vital in the development of periodontal disease. Moreover, PDLSCs are the most effective cell type to be used for periodontium regeneration. This review focuses on changes in PDLSCs, their basic biological behavior, osteogenic differentiation, and drug effects caused by the inflammatory microenvironment, to provide a better understanding of the influence of these factors on periodontal tissue homeostasis. In addition, we discuss the underlying mechanism in detail behind the reciprocal responses of PDLSCs that affect the microenvironment.
Humans ; Periodontal Ligament ; Osteogenesis ; Stem Cells ; Periodontitis/metabolism* ; Cell Differentiation/physiology* ; Cells, Cultured

Objective:To analyze the response of patients with chronic obstructive pulmonary disease (COPD) with multiple and few symptoms to different inhalation drugs, including acute exacerbation and symptom changes.Methods:This study was a multi center, retrospective Cohort study. The subjects of this study were patients with chronic obstructive pulmonary disease in stable stage in 12 hospitals in Hunan and Guangxi from December 2016 to February 2022. Demographics data, lung function, Chronic Obstructive Pulmonary Disease Assessment test questionnaire (CAT) score, modified British Medical Research Council dyspnea questionnaire (mMRC) score and inhalation drug scheme of patients were collected. According to the CAT and mMRC scores, patients were divided into a multi symptom group (CAT≥10 points or mMRC≥2 points) or a few symptom group (CAT<10 points and mMRC<1 point); Subsequently, they were divided into four subgroups based on the inhalation drug regimen: long-acting anticholinergic drugs (LAMA) group, long-acting β2-receptor agonists (LABA)+ inhaled corticosteroids (ICS) group, LABA+ LAMA group, and LABA+ LAMA+ ICS group. All patients were followed up for 1 year, with minimum clinical improvement (MCID) defined as a decrease of ≥2 points in the patient′s CAT score at 6 months, and clinical symptom deterioration (CSD) defined as an increase of ≥2 points in the patient′s CAT score at 6 months.Results:A total of 929 patients with chronic obstructive pulmonary disease were included, including 719(77.4%) with multiple symptoms and 210(22.6%) with few symptoms. There was no statistically significant difference in MCID, CSD, acute exacerbation, hospitalization frequency, and mortality rate among subgroups of asymptomatic COPD patients treated with different inhalation drug regimens (all P>0.05). Among patients with multiple symptoms of chronic obstructive pulmonary disease, compared to those who use LAMA or LABA+ ICS, those who used LABA+ LAMA or LABA+ LAMA+ ICS were more likely to obtain MCID and had a more significant improvement in CAT scores, and the risk of acute exacerbation is lower (all P<0.05). Conclusions:Lesser symptomatic COPD patients should receive single drug LAMA as the initial inhalation treatment drug, while multi symptomatic COPD patients should receive LABA+ LAMA as the initial inhalation treatment drug.

Objective:To explore the predictive value of exhaled nitric oxide (FeNO) for the risk of acute exacerbation in stable chronic obstructive pulmonary disease (COPD) patients over the next year and evaluate whether it can guide the use of inhaled corticosteroids (ICS).Methods:This study was a multicenter, retrospective and observational cohort study. The subjects of this study were stable COPD patients who were hospitalized in 12 hospitals in Hunan Province and Guangxi from January 2017 to December 2021. The patient′s basic Demography information, previous acute exacerbation history, pulmonary function, FeNO, chronic obstructive pulmonary disease assessment test questionnaire (CAT) score, modified British Medical Research Council dyspnea questionnaire (mMRC) score, chronic obstructive pulmonary disease control questionnaire (CCQ) score, and detailed treatment plan were collected. Based on FeNO 25 ppb, patients were divided into a high FeNO group and a normal FeNO group. All patients were followed up for 1 year and information on acute exacerbation was recorded.Results:A total of 825 patients were included, aged (63.5±9.1)years, with a median of 25 ppb of FeNO. A number of 825 patients were followed up for 1 year, of which 262(31.8%) experienced acute exacerbation. Multivariate logistic regression found that FeNO, CAT score, smoking cessation, and past history of acute exacerbation were independent factors predicting acute exacerbation in COPD patients in the next year (all P<0.05). High FeNO was a protective factor for acute exacerbation in COPD patients in the next year, with an OR value of 0.10 ( P<0.001). Further analysis found that the proportion of patients in the high FeNO group using ICS was significantly higher than that in the normal FeNO group [58.8%(247/420) vs 48.6%(197/405), P=0.003]. In the high FeNO group, using ICS can reduce the incidence of acute exacerbation of COPD in the next year [8.9%(22/247) vs 15.6%(27/173), P<0.05], while in the normal FeNO group, there was no statistically significant difference in the frequency of acute exacerbation between patients using ICS and those not using ICS ( P>0.05). Conclusions:FeNO is an independent factor predicting the acute exacerbation of COPD in the next year, and patients with high FeNO levels may consider using ICS in combination.