ObjectiveTo investigate the role of runt-related transcription factor 3 （RUNX3） in transforming growth factor-β₁ （TGF-β₁）-induced activation of mouse primary pulmonary fibroblasts （PFs）， and its effects on fibroblast activation protein （FAP） expression， cell proliferation， and collagen synthesis. MethodsPFs were isolated from C57BL/6 mice and cultured. A RUNX3 knockdown model was established using small interfering RNA （siRNA）. Cells were assigned to the control group （Control）， TGF-β₁-treated group （TGF-β₁）， negative control group （TGF-β₁+siRNA-NC）， and RUNX3-silenced group （TGF-β₁+si-RUNX3）. In addition， a RUNX3 overexpression rescue experiment was performed based on TGF-β₁ stimulation. Protein and mRNA levels of RUNX3， FAP， and typeⅠcollagen （COL1A1） were measured by Western blot and reverse transcription quantitative real-time PCR （RT-qPCR）. Cell proliferation was assessed using CCK-8 and EdU assays. Co-expression of COL1A1 and FAP was examined by double immunofluorescence staining. ResultsCompared with the Control group， RUNX3， FAP， and COL1A1 expression levels were upregulated in PFs in the TGF-β₁ group （P<0.01）. The CCK-8 assay showed that the absorbance value was reduced in the RUNX3 knockdown group compared with the negative control group （P<0.01）. Consistently， the EdU assay demonstrated a lower proportion of EdU-positive cells in the RUNX3 knockdown group than in the negative control group （P<0.01）. Immunofluorescence double staining revealed decreased fluorescence intensities of COL1A1 and FAP in the RUNX3 knockdown group relative to the negative control. Under RUNX3 overexpression conditions， these fluorescence signals exhibited a partial rebound （P<0.01）. ConclusionRUNX3 in TGF-β1-induced PFs may promote cell proliferation and collagen synthesis by positively regulating FAP expression. Targeting the RUNX3/FAP axis may represent a potential therapeutic strategy for pulmonary fibrosis.

ObjectiveTo investigate the effects of targeted silencing of Runt-related Transcription Factor 3 （RUNX3） on the proliferation and migration of Mouse Hepatic Stellate Cells （HSCs）， as well as subsequent collagen deposition. MethodsMouse hepatic stellate cell line （JS-1） was selected and then morphologically observed and identified under a microscope. After the cells had fully adhered， they were treated with 5 ng/mL of transforming growth factor beta 1 （TGF-β₁） for 24 hours to induce hepatic stellate cell activation. Furthermore， a RUNX3 silencing model was established using RUNX3 lentiviral infection. The experiment was divided into four groups： Control group， TGF-β₁ group， TGF-β₁+siRNA-NC group， and TGF-β₁+siRNA-RUNX3 group. Protein expression changes of RUNX3， alpha-smooth muscle actin （α-SMA）， and Alpha 1 type I collagen （Collagen I） were detected using Western blot method. Cellular immunofluorescence assays were employed to investigate the deposition changes of α-SMA and RUNX3 in hepatic stellate cells. RT-qPCR was utilized to examine the mRNA expression changes of RUNX3， α-SMA， and Collagen I. The proliferative capacity of hepatic stellate cells was assessed using Edu staining. The migratory ability of hepatic stellate cells was evaluated through wound healing assays and Transwell migration experiments. ResultsCompared with Control group， a significant elevation in RUNX3 was observed in the TGF-β₁-induced activated HSCs （P<0.01）. Meanwhile， the protein and mRNA levels of fibrosis-related markers and α-SMA and Collagen I were significantly upregulated （P<0.001）. Additionally， the proliferation and migration capabilities of HSCs were significantly enhanced （P<0.001）. In contrast， when compared to TGF-β₁+siRNA-NC group， TGF-β₁+siRNA-RUNX3 group exhibited a notable decrease in RUNX3 and other related indicators， such as the protein and mRNA levels of α-SMA and Collagen I （P<0.05）. Concurrently， the proliferation and migration capabilities of HSCs were significantly inhibited in TGF-β₁+siRNA-RUNX3 group （P<0.01）. ConclusionSilencing RUNX3 can inhibit the deposition of collagen and the proliferation and migration of hepatic stellate cells. Conversely， RUNX3 promotes the proliferation and migration capabilities of HSCs， thereby facilitating the activation of HSC.

ObjectiveTo construct and validate a clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure （CHF），aiming to assist clinical diagnosis and provide tools and methods for individualized treatment of CHF. MethodsThe clinical data of patients with chronic heart failure treated at Dongzhimen Hospital of Beijing University of Chinese Medicine from January 2022 to January 2024 were retrospectively collected. The patients were randomly divided into a training group and a validation group with a ratio of 7∶3. First， the least absolute shrinkage and selection operator （LASSO） regression analysis was used to preliminarily screen the predictive factors affecting the diagnosis of Qi deficiency and blood stasis syndrome in CHF. Subsequently， the Logistic regression method was applied to conduct a more in-depth and detailed analysis of these factors. Variables with P<0.05 in the results of the multi-factor Logistic regression were carefully selected and included. Based on the regression coefficients obtained from this analysis， a model was constructed， and a nomogram was accurately drawn. Using R software，the receiver operating characteristic （ROC） curve，calibration curve，and decision curve analysis （DCA） were precisely drawn. These analyses were used to comprehensively evaluate the model from three crucial aspects： discrimination，calibration，and clinical applicability. Additionally， the accuracy，specificity，sensitivity，positive predictive value，and negative predictive value of the model were meticulously calculated to conduct a more all-round and comprehensive assessment. ResultsIn total， 168 cases were successfully obtained in the training group， and 71 cases were included in the validation group. After a thorough comparison， it was found that there were no statistically significant differences in the baseline data between the two groups. After being rigorously screened by the LASSO-multivariate logistic regression method， dark red tongue，smoking history，cardiac troponin I，and N-terminal pro-B-type natriuretic peptide （NT-ProBNP） were identified as the influencing factors for diagnosing patients with the Qi deficiency and blood stasis syndrome in CHF. The constructed model demonstrated an area under the curve （AUC） of 0.812 in the training group and 0.719 in the validation group. The calibration curve showed that the predicted curve of the model was close to the actual observed curve. DCA indicated that the model could provide substantial clinical benefits for patients at the decision thresholds ranging from 0.2 to 0.9. ConclusionThe clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure constructed in this study shows good performance. It has certain application value in clinical practice， which may contribute to the improvement of the diagnosis and treatment of CHF patients with this syndrome.

Objective: To investigate the effect of targeted silencing of DNA methyltransferase 3A(DNMT3A) on collagen deposition, proliferation and migration activity of mouse lung fibroblasts(PFs). Methods: In order to ensure the proliferation and migration activity of primary fibroblasts, the lung tissues of neonatal C57 suckling mice were taken, PFs were extracted after being sheared, and the morphology was observed and identified under the microscope. PFs cells were activated by 5 ng/ml TGF-β1for 24 h after cell attachment, and DNMT3A silencing model was constructed by small interfering RNA; The experiment was divided into control group, TGF-β1group, TGF-β1+ siRNA-NC group and TGF-β1+ siRNA-DNMT3A group. The protein expressions of DNMT3A, α-smooth muscle actin(α-SMA) and Collagen Ⅰ were detected by Western blot; Real time quantitative reverse transcription polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression changes ofDNMT3A,α-SMAandCollagenⅠ. The proliferation ability of PFs was detected by CCK-8 and EdU staining; the migration ability of PFs was detected by scratch test and Transwell migration test. Results: Compared with the control group, TGF-β1induced the increase of DNMT3A in the activated PFs cell group(P<0.01), the protein and mRNA levels of fibrosis and proliferation related indicators α-SMA and Collagen Ⅰ also increased(allP<0.05), and the proliferation and migration ability of PFs increased(allP<0.000 1). Compared with the siRNA-NC group, the protein expression levels of DNMT3A(P<0.000 1) and related indicators α-SMA(P<0.01) and Collagen Ⅰ(P<0.01) significantly decreased in the DNMT3A silencing group by Western blot, and the mRNA levels ofDNMT3A,α-SMAandCollagenⅠby RT-qPCR also decreased(allP<0.001), and the proliferation(P<0.01) and migration ability(P<0.05) of PFs cells decreased compared with the control group. Conclusion Silencing DNMT3A can inhibit the deposition of collagen and the proliferation of PFs. DNMT3A can promote the proliferation and migration of PFs, and then promote the activation of PFs and the development of pulmonary fibrosis. This process may be regulated by DNA methylation modification.

Objective:To investigate the clinical efficacy and safety of ultrasonic bone scalpel in nasal osteotomy.Methods:A retrospective analysis was conducted on clinical data from the patients who received ultrasonic bone scalpel-assisted nasal osteotomy in the Nasal Plastic & Reconstructive Surgery Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2023 and April 2024. All patients underwent open lateral approach osteotomy using an ultrasonic bone scalpel under direct vision, combined with augmentation rhinoplasty using autologous costal cartilage grafting. Intraoperatively, the nasal dorsum was fully exposed, and the lateral nasal cartilage was separated from the nasal septum, followed by precise bone tissue incision using the ultrasonic bone scalpel. Parameters recorded included operative time, and postoperative complications. Based on the standardized photographs taken before the operation and during the 6-month follow-up after the operation, the observer global aesthetic improvement scale (GAIS) was evaluated by a third-party doctor, with a score ranging from 1 to 5. The smaller the score, the more significant the improvement compared to before the operation. The satisfaction of patients with the surgical outcome was evaluated and classified into four levels: very satisfied, satisfied, dissatisfied, and very dissatisfied.Results:A total of 25 female patients were enrolled, aged 20 to 38 years, with an average age of 27.1 years. All procedures were completed successfully, with a mean operative time of (25.4±4.2) minutes. Postoperative localized swelling of varying degrees was observed. Follow-up ranged from 6 to 18 months, with nasal contour and curvature stabilizing by 6 months postoperatively. No complications, such as infection, nasolacrimal duct, lacrimal sac, medial canthal ligament, nerve injuries, or sensory disturbances, were reported. Two cases exhibited mild nasal bone widening at the 6-month follow-up, though no surgical revision was requested. Significant improvement in external nasal morphology was achieved in all patients, with high satisfaction rates. The patients satisfaction survey showed that 18 cases (72%) were very satisfied and 7 cases (28%) were satisfied with the surgical outcome. GAIS scores reflected positive evaluations [(1.24±0.51) points].Conclusion:The ultrasonic bone scalpel for nasal osteotomy offers the advantages of high-precision cutting and efficient hemostasis. It is highly effective in reshaping the nasal contour, with shorter osteotomy time, reduced intraoperative bleeding, and a lower postoperative complication rate. This study provides some insights into plastic surgeons in optimizing nasal bone modification strategies.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To explore the clinical efficacy of double tract reconstruction and single flap valvuloplasty technique in laparoscopic proximal gastrectomy.Methods:A retrospective cohort study was adopted to analyze the clinical data of 65 patients with gastric cancer who underwent radical proximal gastrectomy at Taizhou People's Hospital Affiliated to Nanjing Medical University from July 2019 to April 2024. According to the different reconstruction methods, the patients were divided into the double tract reconstruction group (double tract; n=43) and oblique anastomosis of esophageal-gastric mucosal window with single flap valvuloplasty technique group (single flap n=22). The baseline data, surgical and postoperative recovery indicators, postoperative pathological results, gastroesophageal reflux at postoperative 6 months, and nutritional status at postoperative 1 year were compared between the two groups. Results:Comparisons of operative time, gastrointestinal reconstruction time, number of lymph nodes dissected, postoperative intestinal function recovery time, total protein, plasma albumin, hemoglobin, and lymphocyte count at 1 week postoperatively, prognostic nutritional index (PNI), time to normalization of postoperative white blood cell count and C-reactive protein, length of hospital stay, hospital costs, and incidence of postoperative pulmonary infection or anastomotic leakage between the two groups showed no statistically significant differences (all P>0.05). However, compared with the double tract group, the single muscle flap group had significantly higher intraoperative blood loss ( P<0.001), higher maximum postoperative body temperature ( P=0.004), and a significantly higher proportion of patients with pleural effusion ≥2 cm ( P=0.029).No statistically significant differences were observed between the two groups in terms of tumor length, length of esophageal involvement, Siewert classification, tumor differentiation degree, neural invasion, lymphovascular invasion, number of metastatic lymph nodes, tumor T stage and N stage, or UICC TNM staging for gastric cancer (all P>0.05). Nevertheless, the minimum distance of the lower resection margin in the double tract group was significantly longer than that in the single muscle flap group, with a statistically significant difference between the groups ( P<0.001). At 6 months postoperatively, results from the Quality of Life Questionnaire-Core 30 (QLQ-C30), Quality of Life Questionnaire-Stomach 22 (QLQ-ST022), Reflux Symptom Index scores, Visick grading, and gastroscopy (Los Angeles classification) all indicated that the incidence of reflux esophagitis in the double tract group was significantly lower than that in the single muscle flap group (all P<0.001). Gastrointestinal contrast examination showed no anastomotic stenosis in either group; gastroesophageal reflux occurred in 5 cases (11.6%) in the double tract group and 4 cases (18.2%) in the single muscle flap group, with no statistically significant difference (χ2=0.524, P=0.469). Gastroscopy results revealed that the incidence of reflux esophagitis at 6 months postoperatively was 9.3% (4/43) in the double tract group and 59.1% (13/22) in the single muscle flap group, with a statistically significant difference between the two groups (χ2=18.680, P<0.001).At 1 year postoperatively, the dual-chamber group showed better performance in body mass index(BMI), proportion of a decrease in BMI, plasma albumin, and PNI compared with the single muscle flap group, with statistically significant differences (all P<0.05). There were no statistically significant differences in hemoglobin or lymphocyte count between the two groups (all P>0.05). During 1 year of follow-up, one case of anastomotic recurrence occurred in each group, with no statistically significant difference between the groups ( P=0.624). Conclusions:Both proximal gastrectomy with double-tract anastomosis and esophagogastric mucosal window oblique anastomosis combined with single muscular flap valvuloplasty for digestive tract reconstruction are safe and feasible. However, double-tract anastomosis can better prevent the occurrence of postoperative reflux esophagitis, improve the patient's postoperative nutritional status, and enhance the patient's quality of life.

Aim To investigate the effects of edaravone(EDA)on depression-like behaviors in a rat model of post-stroke depression(PSD)and to explore the un-derlying mechanisms.Methods SD rats were ran-domly divided into:sham operation group(Sham),cerebral ischemia group(CI),post-stroke depression(PSD),fluoxetine(10 mg·kg-1)group,and EDA(5,15 mg·kg-1)group.A PSD rat model was estab-lished using the suture method combined with 56 d of chronic unpredictable mild stimulation.Drug treatment was given once daily for 28 d after stimulation.Body weight and sucrose water preference were measured during the stimulation period,and serum TNF-α,IL-1 β,IL-6,MDA,SOD levels,and hippocampal tissue HO-1 and GPX4 protein expression were detected at the end of stimulation.Results Compared with the sham group,the rat neurological function scores of the remaining groups increased(P＜0.01).Compared with the PSD group,EDA increased the body weight and sucrose water preference of the rats(P＜0.01),significantly decreased the serum TNF-α,IL-1β and IL-6 levels,decreased the MDA level,increased the SOD level(P＜0.01),and up-regulated hippocampal HO-1 and GPX4 protein expression(P＜0.01).Con-clusions EDA improves depression-like behaviors and inhibits peripheral inflammation and oxidative stress in-jury in PSD rats,and its mechanism may be related to the activation of HO-1/GPX4 pathway to inhibit oxida-tive stress.

Objective:To analyze the current status and trend of the mortality burden of cardiovascular disease in China from 2010 to 2021.Methods:Data related to cardiovascular disease mortality and disability-adjusted life year (DALY) were extracted from the Global Burden of Disease Study 2021 (GBD2021) database. The age-standardized mortality rate and DALY rate were calculated, using the 2021 world standard population estimated by GBD2021. Joinpoint 5.2.0 software was used to calculate the mortality rate, standardized mortality rate, DALY rate, standardized DALY rate, annual percent change (APC), average annual percent change (AAPC), and 95% CI of cardiovascular disease in China from 2010 to 2021. Results:The mortality rate of cardiovascular disease was 357.44/100 000, and the age-standardized mortality rate was 280.11/100 000 in China in 2021. The DALY rate was 7 043.33/100 000, and the age-standardized DALY rate was 5 120.06/100 000. From 2010 to 2021, the mortality rate and DALY rate of cardiovascular disease in China showed an upward trend (AAPC was 1.58% and 0.83%, respectively, both P<0.05), and the standardized mortality rate and standardized DALY rate showed a downward trend (AAPC was -2.13% and -2.02%, respectively, both P<0.05). The mortality burden of cardiovascular disease was higher in males (mortality rate 392.80/100 000, DALY rate 8 156.19/100 000) than in females (mortality rate 320.38/100 000, DALY rate 5 876.87/100 000). With the increase older in age, the mortality burden of cardiovascular disease in China decreased first and then increased. China ranked high in the mortality burden of cardiovascular disease among G20 member countries. Conclusions:The death burden of cardiovascular disease is serious in China. The mortality rate and DALY rate of cardiovascular disease in China showed an increasing trend from 2010 to 2021, and the standardized mortality rate and standardized DALY rate of cardiovascular disease ranked high in G20 member countries. The death burden of cardiovascular disease was more serious in men and the elderly. It is necessary to develop more comprehensive prevention, treatment, and rehabilitation measures for men and the elderly to reduce mortality and disability rates, decrease the disease burden, and improve the quality of life.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.