Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

(+)-Strebloside, a significant bioactive compound isolated from the roots of Streblus asper Lour., demonstrates inhibitory effects against multiple malignancies. However, its specific function and underlying mechanistic pathways in Non-Hodgkin lymphoma (NHL) remain unexplored. This investigation sought to elucidate the role and potential mechanisms of (+)-strebloside-induced NHL cell death. The results demonstrated that (+)-strebloside significantly induced apoptosis and ferroptosis in NHL cells, including those from Raji cell-derived xenograft models. Mechanistic analyses revealed that (+)-strebloside enhanced six-transmembrane epithelial antigen of prostate 3 (STEAP3)-induced ferroptosis in NHL, and STEAP3 inhibition reduced the proliferation-inhibitory effects of (+)-strebloside. Furthermore, (+)-strebloside suppressed NHL proliferation through the mitogen-activated protein kinase (MAPK) pathway, and extracellular signal-regulated kinase (ERK) inhibition diminished the proliferation-inhibitory activity induced by (+)-strebloside. These findings indicate that (+)-strebloside presents promising therapeutic potential for NHL treatment.
Humans ; Ferroptosis/drug effects* ; Lymphoma, Non-Hodgkin/physiopathology* ; Cell Line, Tumor ; MAP Kinase Signaling System/drug effects* ; Animals ; Cell Proliferation/drug effects* ; Mice ; Apoptosis/drug effects* ; Membrane Proteins/genetics* ; Xenograft Model Antitumor Assays ; Male ; Mice, Nude

OBJECTIVE: To investigate the correlation between postoperative driving pressure (DP) and the prognosis of lung transplantation, and to further evaluate the value of early DP monitoring in lung transplantation. METHODS: A observational study was conducted. The patients after lung transplantation who admitted to the intensive care unit (ICU) of Wuxi People's Hospital from February 1, 2022 to February 1, 2023 were collected. They were divided into low DP group (DP≤15 cmH₂O, 1 cmH₂O ≈ 0.098 kPa) and high DP group (DP > 15 cmH₂O) according to DP within 2 hours after operation. The clinical data including general information, primary disease, chronic diseases, cardiopulmonary function, laboratory indicators, intraoperative condition, postoperative lactic acid (Lac) and ventilator parameters were collected. Primary outcomes included 28-day and 90-day survival, and secondary outcomes included occurrence of primary graft dysfunction (PGD), duration of extracorporeal membrane oxygenation (ECMO), duration of mechanical ventilation, weaning of mechanical ventilation, and length of ICU stay. The general data and observations between the two groups were compared. Kaplan-Meier curve analysis was conducted to analyze the situation of mechanical ventilation and 90-day survival. Receiver operator characteristic curve (ROC curve) was used to evaluate the predictive ability of DP for failed weaning of mechanical ventilation and 90-day death. The dose-response relationship between DP and 90-day death risk was determined by restricted cubic spline model. Univariate analysis was performed using Cox proportional hazards model. RESULTS: A total of 101 patients were enrolled, with 68 patients (67.3%) in the low DP group and 33 patients (32.7%) in the high DP group. No statistically significant difference in general information, chronic diseases, primary diseases, cardiopulmonary function, laboratory indicators, intraoperative conditions, and postoperative Lac between the two groups was found. Compared with the low DP group, the patients in the high DP group had higher inspiratory pressure (Pinsp) and incidence of PGD with grade 3 at 24 hours after operation [Pinsp (cmH₂O): 21.0±0.6 vs. 20.0±0.7, PGD with grade 3 at 24 hours: 60.6% (20/33) vs. 39.7% (27/68), both P < 0.05], longer duration of ECMO, duration of mechanical ventilation, and the length of ICU stay [duration of ECMO (hours): 37 (21, 109) vs. 22 (14, 43), duration of mechanical ventilation (days): 3.1 (1.8, 10.7) vs. 1.9 (1.1, 3.2), length of ICU stay (days): 6 (3, 13) vs. 4 (3, 5), all P < 0.05], and lower successful weaning rate of mechanical ventilation [81.8% (27/33) vs. 95.6% (65/68), P < 0.05). The 28-day and 90-day survival rates in the high DP group were significantly higher than those in the low DP group [28-day: 69.7% (23/33) vs. 86.8% (59/68), 90-day: 63.6% (21/33) vs. 83.8% (57/68), both P < 0.05]. Kaplan-Meier curve showed that the patients in the low DP group were weaned and extubated earlier than high DP group, and the cumulative situation of weaning was better (Log-Rank test: χ ² = 14.054, P < 0.001), and the 90-day cumulative survival rate in the low DP group was significantly higher than that in the high DP group (Log-Rank test: χ ² = 4.791, P = 0.029). ROC curve analysis showed that the area under ROC curve (AUC) of DP for predicting 90-day death was 0.664 [95% confidence internal (95%CI) was 0.540-0.787, P = 0.017], and the AUC for predicting failed weaning of mechanical ventilation was 0.794 (95%CI was 0.667-0.921, P = 0.004). Results of restricted cubic spline model analysis showed that the 90-day death risk continued to increase with the DP < 18 cmH₂O; when DP≥18 cmH₂O, elevated DP did not continue to increase the 90-day death risk, showing a plateau effect. Univariate analysis showed that DP was independent risk factors of 90-day death, and the death risk increased by 9.3% for every 1 cmH₂O increase in DP [hazard ratio (HR) = 1.093, 95%CI was 1.007-1.186, P = 0.033]. CONCLUSIONS DP is an independent risk factor of death after lung transplantation, and early postoperative DP may be used as a predictor of failed weaning of mechanical ventilation and 90-day death after lung transplantation.
Humans ; Lung Transplantation ; Prognosis ; Respiration, Artificial ; Intensive Care Units ; Postoperative Period ; Pressure ; Primary Graft Dysfunction/epidemiology* ; Transplant Recipients ; Female ; Extracorporeal Membrane Oxygenation ; Male ; ROC Curve ; Middle Aged

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Objective: To find any differentially expressed circRNAs in oral leukoplakia (OLK) and oral lichen planus (OLP), to investigate the possible role of circRNAs in the pathogenesis of these two diseases. Methods: This study obtained hospital ethical approval. High-throughput sequencing was used to detect differentially expressed circRNAs in OLK, OLP, oral squamous cell carcinoma and normal oral mucosal tissues. CircRNAs were verified by qRT-PCR, enzyme tolerance assays and Sanger sequencing. GO functional analysis and KEGG pathway analysis were performed to predict the functions of circRNAs in OLP. TargetScan and miRanda were applied to predict targeted miRNAs and mRNAs of circRNAs, and ceRNA networks were mapped. Results: A total of 49 circRNAs were differentially expressed in OLK and OLP together, including 30 upregulated and 19 downregulated circRNAs. The five circRNAs confirmed with RT-qPCR, including circHLA-C, circRNF13, circTTN, circSEPN2 and circALDH3A2, were all abnormally expressed in OLK and OLP, among which circHLA-C was a key circRNA with trans splice sites, which was validated by expanding the sample size. ROC curve analysis showed that the area under the circHLA-C curve for predicting OLK was 0.955, and the area under the circHLA-C curve for predicting OLP was 0.988. GO functional analysis showed enrichment of many biological processes related to the immune process. The KEGG pathway with the highest enrichment score was "Natural killer cell mediated cytotoxicity". HLA-C was significantly enriched in these processes/pathways. CeRNA network analysis showed that circHLA-C interacted with a variety of miRNAs, such as hsa-miR-26a-5p, hsa-miR-129-5p, and hsa-miR-29a-3p. Conclusion Many circRNAs were differentially expressed in both OLK and OLP, circHLA-C being the most elevated. CircHLA-C is valuable for the early diagnosis of OLK and OLP and may serve as a potential biomarker for the diagnosis and prognosis of OLK and OLP.

Objective:To explore the teaching effect and novel ideas of online teaching applied in skill operation course.Methods:One hundred and fifty-one students studying in Sichuan University taking the First Aid in the Life: Basic Knowledge and Skills as an elective course in the autumn semester of 2019 and spring semester of 2020 were included as the research subjects in this study. Among them, 77 students in the spring semester of 2020 were selected as the experimental group and 74 students in the autumn semester of 2019 were selected as the control group. The students in the experimental group studied the first aid course by online platform, and the others in the control group studied through traditional teaching mode. The teaching effect of the two groups was compared and the teaching satisfaction of the two groups weas analyzed. SPSS 23.0 was used for Chi-square test and t-test. Results:There was no significant difference between the control group and the experimental group in the assessment scores of cardiopulmonary resuscitation, hemostatic bandaging, and fracture fixation [(8.65±0.81 vs 8.69±0.90, P=0.750); (8.10±0.50 vs 8.12±0.61, P=0.880); (8.21±0.89 vs 8.16±0.78, P=0.710)]. Among the students participating in the questionnaire survey in the experimental group, 59 (95.16%) students thought that this course was helpful in dealing with first aid in daily life, and 38 (61.29%) students did not want to change the traditional teaching method to online teaching. Conclusion:The application of online teaching in first-aid skill operation course is feasible and can achieve the similar teaching effect, which provides a novel idea for exploring the online teaching of first aid skills.

Objective:To investigate the main postoperative complications, causes of death and the risk factors for survival in patient with benign end-stage lung diseases within 1 year after lung transplantation.Methods:A retrospective analysis was conducted to collect the clinical data of 200 patients with benign end-stage lung disease who underwent lung transplantation admitted to Wuxi People's Hospital Affiliated to Nanjing Medical University from May 2017 to October 2018. The main postoperative complications, survival and causes of death within 1 year after operation were analyzed. The Kaplan-Meier method was used to plot survival curves, and the Log-Rank test was used to compare the influence of factors, including recipient's gender, use of marginal donor lung, primary disease, preoperative combination of moderate to severe pulmonary hypertension (PAH), intraoperative extracorporeal membrane oxygenation (ECMO) support, surgical methods, intraoperative massive blood loss, postoperative complications [infection, primary graft dysfunction (PGD), acute rejection], on 1-year survival in patients who underwent lung transplantation. The multivariate Cox proportional hazards regression model was used to evaluate the risk factors of death within 1 year after lung transplantation.Results:Two hundred patients underwent successful lung transplantation. The major postoperative complications within 1 year after transplantation included infection in 131 patients, PGD in 20 patients, acute rejection in 57 patients, anastomotic complication in 26 patients and others (new onset diabetes, osteoporosis, etc.) in 53 patients. The 3-month, 6-month, and 1-year postoperative cumulative survival rates were 81.5%, 80.0% and 77.5%, respectively. Forty-five patients died during 1 year after operation, among whom 14 died of infection, 7 died of PGD, 8 died of acute rejection, 4 died of anastomotic complication, 3 died of cardio-cerebrovascular accident, 3 died of multiple organ failure, 2 died of respiratory failure and 4 died of other causes (traffic accident, etc.). The Kaplan-Meier survival analysis showed that recipient's gender, idiopathic pulmonary fibrosis (IPF) as the primary disease, preoperative combination of moderate and severe PAH, intraoperative ECMO support, intraoperative massive blood loss, postoperative complications (infection, PGD, acute rejection) were influencing factors for postoperative 1-year survival rate. The multivariate Cox regression model showed that male was the protective factor [hazard ratio ( HR) = 0.481, 95% confidence interval (95% CI) was 0.244-0.947, P = 0.034], IPF as the primary disease ( HR = 2.667, 95% CI was 1.222-5.848, P = 0.014), intraoperative use of ECMO support ( HR = 1.538, 95% CI was 0.787-3.012, P = 0.028), massive blood loss during surgery ( HR = 2.026, 95% CI was 0.976-4.205, P = 0.045) and postoperative infection ( HR = 3.138, 95% CI was 1.294-7.608, P = 0.011), PGD ( HR = 1.604, 95% CI was 0.464-5.539, P = 0.004), and acute rejection ( HR = 1.897, 95% CI was 0.791-4.552, P = 0.015) were the independent risk factors for death within 1 year after transplantation. Conclusions:One-year survival rates after lung transplantation are affected by recipient's gender, primary disease, preoperative combination of moderate and severe PAH, intraoperative ECMO support, intraoperative massive blood loss, and postoperative complications (infection, PGD, acute rejection). The male is the protective factor, while IPF as the primary disease, intraoperative ECMO support, massive blood loss during surgery and postoperative complications (infection, PGD, acute rejection) are independent risk factors for death within 1 year after lung transplantation.

Objective To optimize the process of ultrasonic extraction of polysaccharide in Anoectochilus roxburghii and to investigate the method of protein removal. Methods The extraction rate of polysaccharide was used as the detection index. On the basis of single factor investigation, Box-Behnken experimental design and response surface method were used to optimize the three factors of material-liquid ratio, ultrasonic time and ultrasonic extraction temperature. The five deproteinization methods including Sevage reagent method, TCA method, salt method (NaOH-CaCl₂ and NaOH-NaCl) and hydrochloric acid method were investigated with the retention rate of polysaccharide and protein removal rate. Results The optimal extraction conditions of polysaccharide from Anoectochilus roxburghii were as follows: liquid-to-solid ratio was 10∶1, extraction temperature was 48 ℃ and extraction time was 36 min with extraction 2 times, ultrasonic power was 300 W, the extraction rate was 13.13%. NaOH-CaCl₂ deproteinized methods∶ the loss rate of polysaccharide was 18.74%, and the removal rate of protein was 95.62%. Conclusion Ultrasonic extraction is easy to operate, and the optimized extraction method can achieve a high extraction rate. NaOH-CaCl₂ deproteinization methods can get high protein removal rate and polysaccharide retention rate. This method is suitable for the research and development of the active components of the polysaccharides from Anoectochilus roxburghii.

Objective:To study the level and deficiency of 25-hydroxy vitamin D [25-(OH)D] in 7215 pregnant women in Dalian district, and provide a scientific evidence for the prevention of vitamin D deficiency and reasonable supplementation.Methods:During January to December of 2018, the basic information and blood samples of 7215 pregnant were collected in Maternal and Child Health Care hospital of Dalian. The level of serum 25-hydroxy vitamin D was detected by chemiluminescence method. All data was analyzed by SPSS 17.0 software.Results:In Dalian district, the average level of serum 25-(OH)D in 7215 pregnant women was 22.74(16.02, 28.62) ng/ml, and the deficiency rate of vitamin D was 33.89%, and the severe deficiency rate was 6.68%. The average level of serum 25-(OH)D in pregnant women aged 18-24 years old, 25-34 years old and 35-45 years old were 20.22(13.61, 25.57) ng/ml, 22.75(16.12, 28.42) ng/ml and 23.60(16.76, 29.92)ng/ml, respectively. With the increasing of pregnant age, the level and the deficiency rate of serum 25-(OH)D was gradually rising with significant difference( P<0.01), and the highest deficiency rate was pregnant aged 18~24 years old with 42.40%. Conclusion:The level of vitamin D of pregnant women in Dalian district was insufficient status, especially for young pregnant women. Health education for vitamin D deficiency should be focused on young pregnant women.

Objective:To explore the clinical characteristics of one living-related kidney transplant recipient infected with 2019 coronavirus disease(COVID-19).Methods:The clinical diagnosis and treatment of one living-related kidney transplant recipient after the occurrence of COVID-19 were analyzed retrospectively. Course of onset, clinical manifestations, laboratory and image enamination, outpatient and inpatient therapies and outcomes.Results:The renal transplant recipient was diagnosed as COVID-19(severe) with influenza A virus infection based upon epidemiological survey, clinical manifestations, laboratory examinations, imaging findings and etiological tests. The clinical symptoms were gradually relieved and lung lesions became absorbed after tapering and withdrawing immunosuppressants, antiviral therapy of abidol/oseltamivir, antibiotic therapy, hormonal anti-inflammation, oxygen inhalation, nutritional supports and adequate rest.Conclusions:Living-related kidney transplant recipients have specific immunosuppressive states.The long-term effect of covid-19 on recipients should be determined through long-term follow-ups.