ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ （AngⅡ） and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment， AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h， and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 （CCK-8） to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of B-type natriuretic peptide （BNP） in cell culture supernatant， and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently， the experiment was divided into a blank group （20% blank serum）， a model group （20% blank serum + 5×10^-5 mol·L^-1 AngⅡ）， low-， medium-， and high-dose （5%， 10% and 20%） serum containing Zhenwutang groups， an autophagy inhibitor group （1×10^-4 mol·L^-1 3-MA）， and autophagy inducer group （1×10^-7 mol·L^-1 rapamycin）. The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe （Lyso Tracker） and mitochondrial probe （Mito Tracker） co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect Caspase-3， Caspase-9， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， and cytochrome C （Cyt C） in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase （Parkin）， phosphatase and tensin homolog （PTEN）-induced kinase 1 （PINK1）， and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3， cleaved Caspase-9， Bax， Bcl-2， and Cyt C in apoptosis-related pathways， phosphorylated ubiquitin ligase （p-Parkin）， phosphorylated PTEN-induced kinase 1 （p-PINK1）， p62， and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways， and the change of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10^-5 mol·L^-1， the cell activity was the lowest， and there was no cytotoxicity. At this concentration， the surface area of cardiomyocytes was significantly increased （P<0.01）， and the content of BNP in the supernatant of culture medium was significantly increased （P<0.05）. Therefore， AngⅡ with a concentration of 5×10^-5 mol·L^-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group， the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate （P<0.01） and significantly decreased mitochondrial membrane potential （P<0.01）. The results of immunofluorescence co-localization showed that compared with the blank group， the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group， the relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 in the model group was significantly up-regulated （P<0.01）， while the relative mRNA expression of Bcl-2， Parkin， and PINK1 was significantly down-regulated （P<0.01）. In addition， the relative protein expression of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 was significantly up-regulated （P<0.01）. The LC3Ⅱ/Ⅰ was significantly decreased， and the relative protein expression of Bcl-2， p-Parkin， p-PINK1， and Beclin1 was significantly down-regulated （P<0.01）. Compared with the model group， the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate （P<0.01）， and the decrease ratio of mitochondrial membrane potential is significantly lowered （P<0.01） in a dose-dependent manner. Additionally， both red and green fluorescence spots became more in these groups. In the 3-MA group， the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 was significantly down-regulated （P<0.05， P<0.01）， while that of Bcl-2， Parkin， and PINK1 was significantly up-regulated （P<0.01）. In the serum containing Zhenwutang groups， the relative protein expression levels of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 were significantly down-regulated （P<0.05，P<0.01）. The LC3Ⅱ/Ⅰ was significantly increased， and the relative protein expression levels of Bcl-2， p-Parkin， p-PINK1， and Beclin1 were significantly up-regulated （P<0.01）. ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.

Objective To identify the independent predictors of programmed death-1 (PD-1) inhibitor-related endocrine adverse events and construct a clinically usable risk prediction model. Methods A total of 302 patients with solid tumors treated with PD-1 inhibitors were retrospectively enrolled. According to the presence or absence of endocrine immune-related adverse events (irAEs), the patients were divided into case group and control group. The clinical and laboratory indexes were compared between the two groups. Multivariable logistic regression was used to confirm independent predictors of endocrine irAEs. The nomogram was constructed, while the receiver operating characteristic (ROC) curve was used to test the prediction performance of the model. Results The overall incidence of endocrine irAEs was 21.9% (66/302), and the incidence of hypothyroidism was 19.5% (59/302). The age, PD-1 inhibitors, free thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin, amylase, lymphocyte subset CD3 expression were statistically different between the two groups (P＜0.05). Multivariable logistic regression showed that higher expression of lymphocyte subset CD3 was a protective factor to prevent endocrine irAEs occurrence (P＝0.004), while age＜60 years, higher TPOAb and use of pembrolizumab were independent risk factors of endocrine irAEs (P＜0.05). The nomogram model thus constructed, and when the threshold probability of the model exceeded 0.1, its net benefit was higher. ROC curve showed that the AUC of the model to predict endocrine irAEs was 0.760. The prediction result of the model was highly consistent with the actual result. Conclusions The age, type of PD-1 inhibitor, baseline TPOAb level, and baseline CD3 expression can independently predict endocrine irAEs occurrence or not. The nomogram model based on this model has good predictive efficiency, which can provide reference for early identification of high-risk patients and immunotherapy management.

OBJECTIVES: To analyze the multimorbidity patterns and core diseases among hospitalized patients in different age groups and to explore the impacts of multimorbidity patterns on hospitalization costs. METHODS: Electronic medical records of adult inpatients (aged ≥18 years) from Ningbo Medical Center Lihuili Hospital between January 1, 2018, and June 30, 2023 were collected. The multimorbidity status involving 53 specific diseases was analyzed across different age groups. Association rule mining was used to identify common multimorbidity patterns. Complex network analysis was used to identify core diseases within the multimorbidity networks. Generalized estimating equations (GEE) were used to analyze the impact of different multimorbidity patterns on hospitalization costs. RESULTS: The prevalence of multimorbidity among the 359 402 adult inpatients was 38.51%, with higher rates observed in males (43.60%) and elderly patients (58.29%). Association rule mining identified 15 common multimorbidity patterns, which exhibited differences across age groups. The most prevalent multimorbidity pattern overall was "diabetes→hypertension" (support=7.04%, confidence=62.17%, lift=2.17). In the young adult group, the most prevalent pattern was "dyslipidemia→chronic liver disease" (support=1.19%, confidence=53.17%, lift=6.04). In the middle-aged group, it was "diabetes→hypertension" (support=4.84%, confidence=50.28%, lift=2.15). In the elderly group, it was "coronary heart disease, diabetes→hypertension" (support=2.38%, confidence=77.43%, lift=1.63). Complex network analysis revealed that the core diseases within multimorbidity networks differed across age groups. The core disease identified in the young adult group was chronic liver disease (degree centrality=50, betweenness centrality=0.055, closeness centrality=0.963). Core diseases in the middle-aged group included hypertension, chronic liver disease, and diabetes (all with degree centrality=52, betweenness centrality=0.022, closeness centrality=1.000). Core diseases in the elderly group comprised hypertension, diabetes, malignant tumors, chronic liver disease, thyroid disease, anemia, and arrhythmia (all with degree centrality=52, betweenness centrality=0.009, closeness centrality=1.000). Generalized estimating equations analysis indicated that, most multimorbidity patterns were significantly associated with increased hospitalization costs. However, the magnitude of cost increase varied across different multimorbidity patterns. Specifically, hospitalization costs for patients with patterns such as "heart failure→hypertension", "stroke→hypertension", "malignant tumor, diabetes→hypertension", "stroke, diabetes→hypertension", and "diabetes, heart failure→hypertension" were more than double those of patients without any target diseases. CONCLUSIONS Multimorbidity patterns and core diseases among hospitalized patients differ significantly across age groups, and different patterns exert varying impacts on hospitalization costs. These findings underscore the necessity for age-stratified and multimorbidity pattern specific management strategies.
Humans ; Multimorbidity ; Male ; Hospitalization/economics* ; Female ; Aged ; Middle Aged ; Adult ; Age Factors ; Young Adult ; Adolescent ; Diabetes Mellitus/epidemiology* ; Electronic Health Records ; Aged, 80 and over ; Hospital Costs ; China/epidemiology* ; Hypertension/economics* ; Liver Diseases/epidemiology*

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

Objective:To analyze the efficacy of unilateral arytenoid chondroplasty combined with minimally invasive mucosal flap plasty in the management bilateral vocal cord paralysis.Methods:A total of 66 patients with bilateral vocal cord paralysis hospitalized in the First Hospital of Sun Yat-sen University from January 2018 to December 2023 were retrospectively analyzed, among whom there were 8 males and 58 females, with ages ranging from 35 to 86 years old(mean age (57.8±11.6) years). All patients underwent suspension laryngoscopic CO 2 laser unilateral arytenoid chondroplasty and mucosal flap under general anesthesia. Postoperative follow-up period extended from 6 months to 6 years, with a median duration of 28 months. The study compared the degree of dyspnea and voice quality (subjective and objective evaluation) of the patients pre- and post-operatively, and analyzed the clinical differences between patients with and without preoperative or intraoperative tracheotomy, the extubation rate of tracheotomized patients, the recurrence rate, and the complication rate. Continuous variables conforming to normal distribution were tested by t-test and categorical variables by χ2 test,the Wilcoxon rank-sum test was used to analyze the improvement in dyspnea before and after surgery. Results:Compared with the preoperative period, 59 patients showed improvement in postoperative dyspnea ( U=161.5, P<0.01); there was no significant difference in voice disorder index 10, subjective auditory-perceptual assessment, and maximal vocalization time ( P>0.05), all of which remained within the relative normal range. Tracheotomy was performed in 32 out of 66 patients, with predominantly degree Ⅲ- dyspnea (46.9%, 15/32), including 26 patients with preoperative tracheotomy and 6 patients with intraoperative tracheotomy. Among the 34 patients who did not undergo tracheotomy, the majority presented with degree Ⅱ-dyspnea (82.4%, 28/34). All patients achieved successful extubation following surgery, with a mean median time to extubation of 1 month. Conclusions:The combination of unilateral arytenoid chondroplasty and minimally invasive mucosal flap plasty represents a refined and effective therapeutic approach for bilateral vocal cord paralysis. This minimally invasive technique has the potential to reduce the rate of tracheotomy.

Objective:To monitor intra-fractional set-up errors in tumor radiotherapy using a real-time intelligent capture system for precision displacement.Methods:A simulated radiotherapy environment was created in both the laboratory and the treatment room. A three-axis ( xyz) displacement platform (LD60-LM) and dial gauges were used as displacement measurement tools. Moreover, a real-time intelligent capture system for precision displacement was developed for displacement monitoring. With 23 patients treated with radiotherapy enrolled in this study, the above system was employed to monitor their intra-fractional set-up errors in fractionated radiotherapy. Descriptive analyses were conducted on the deviations between the data captured by cameras and the actual displacement, obtaining the mean values and standard deviation. Results:The monitoring calibration data from the laboratory revealed displacement differences of ≤ 0.5 mm within 20 mm and a maximum displacement difference of 1.47 mm for 50 mm. In contrast, the calibration result from the treatment room exhibited deviations of ± 0.2 mm on the y- z axes, as displayed by both the left and right cameras, and ± 0.31 mm on the x- z axes, as displayed by the middle camera. During 37 radiotherapy sessions in 23 patients, the monitoring result from the middle camera revealed five deviations exceeding the threshold of 5 mm, with the maximum deviation duration and displacement of 57.2 s and 9.24 mm, respectively. Conclusions:The real-time intelligent capture system for precision displacement based on machine vision can achieve real-time monitoring of set-up errors during tumor radiotherapy. Nevertheless, further improvements and service testing are necessary for this system.

Objective To study the changes in peripheral blood T lymphocytes in patients with ankylosing spondylitis and their correlation with the disease's severity and prognosis.Methods We selected 120 patients with ankylosing spondylitis treated between January 2020 and March 2023 as the research group and 120 healthy people who had medical examinations in the same period as the health group.We detected the changes in CD4+,CD8+and CD4+/CD8+values of peripheral blood T lymphocyte subsets with flow cytometry,compared the differences in T lymphocyte subsets between the two groups,and analyzed the correlation with the disease severity of the patients.All the 120 patients with ankylosing spondylitis were followed up for 6 months after treatment to assess their prognosis.General information and T lymphocyte sub-groups CD4+,CD8+level,CD4+/CD8+value changes were compared among patients with different prognosis.We analyzed the value of T lymphocyte sub-groups in predicting the prognosis of patients with ankylosing spondylitis.Results In the research group CD4+and CD4+/CD8+were lower but CD8 1 was higher than those in the healthy group(P＜0.05).CD4+and CD4+/CD8 were lower but CD8+was higher in patients with advanced ankylosing spondylitis than in early and mid-term patients(P＜0.05).The ROC curve analysis showed that the AUC of CD4+,CD8+,and CD4+/CD8+combined diagnosis of ankylosing spondylitis patients was 0.878,with higher diagnostic sensitivity than that of the single diagnosis(P＜0.05).In the poor prognosis group,CD8+was higher than that in the excellent prognosis group,but CD4+and CD4+/CD8 value were lower than the latter(P＜0.05).The results of Pearson test showed that CD4+and CD4+/CD8+were negatively correlated with the prognosis of patients with ankylosing spondylitis(r=-0.568,-0.656,P＜0.001).CD8+was positively correlated with the prognosis of patients with ankylosing spondylitis(r=0.623,P＜0.001).ROC curve analysis showed that the AUC of the combined diagnosis of CD4+,CD8+and CD4+/CD8+for ankylosing spondylitis patients was 0.910,and the diagnostic sensitivity was higher than that of single diagnosis(P＜0.05).Conclusion The abnormal levels of peripheral blood T lymphocyte subsets in patients with ankylosing spondylitis are closely related to the severity and prognosis of the disease,and can be used as a reference indicator for diagnosing the severity and prognosis of ankylosing spondylitis.

In the context of Chinese narrative medicine,narrative thinking is a thinking mode in medical thinking,which is as important as evidence-based thinking,and is also the cornerstone of patient life safety and healthcare quality.Taking"narrative traditional Chinese medicine(TCM)"in the"Chinese narrative medicine discourse system"as the framework,this paper explored the narrative thinking contained in the theory of TCM("observing phenomena to capture essence","acting by combining and integrating","the ease of mind and body","narrative prescription",and"syndrome differentiation and treatment"),the life and health narrative literacy("life-preserving literacy","interpersonal narrative connection awareness"),as well as professional narrative thinking("ability to handle things","ability to deal with things","combination of the four diagnostic methods","treating the disease from its root",and"coordination of body and spirit")possessed by TCM practitioners.Besides,it clarified the important value of narrative thinking in improving healthcare quality,while proposed suggestions for the mechanism of medical education,teaching content,and teaching method based on the concept of Chinese narrative medicine.Looking forward to inspiring more contemporary medical educators and clinical practitioners to value the cultivation of narrative thinking and the practice of narrative medicine.

Objective:To explore the psychological experiences of lung cancer patients during treatment based on the perspective of narrative medicine,and to provide references for targeted nursing interventions.Methods:Guided by the concept of narrative medicine,the phenomenological method of qualitative research was used to conduct in-depth interviews with 20 lung cancer patients.The interview data were analyzed,refined,and summarized by using the content analysis method.Results:From the perspective of the humanistic value of narrative medicine,four themes were extracted from the interview contents with 20 lung cancer patients,including the loss of patients'role identity,the experience of disease uncertainty,the fear and expectation of death,and the helplessness and perception of life.Conclusion:During the treatment process of lung cancer patients,there are negative psychological experiences,such as loss of role identity,uncertainty of disease,fear of death,and hope to leave with dignity.Meanwhile,there are positive perceptions,such as contemplation of the meaning of life and actively coping with it.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.