Bispecific killer cell engagers (BiKEs) are a powerful tool to incite the killing power of natural killer (NK) cells. Here, we posited that the BiKE technology could be utilized to deplete activated immune cells expressing programmed death-1 (PD-1⁺ cells), and hence treat autoimmune diseases since these cells drive the disorders. We designed and generated PD-1 BiKE that targets an activating NK cell receptor, CD16, and PD-1. PD-1 BiKE showed specific binding to PD-1⁺ cells and engaged CD16 simultaneously. PD-1 BiKE enhanced NK cell-mediated apoptosis and depletion of PD-1⁺ Raji cells, but not PD-1^- Raji cells. Further, PD-1 BiKE induced apoptosis of primary PD-1⁺ T lymphocytes that are highly relevant to autoimmune disease progression. The BiKE depleted 42% of primary T cells that were stimulated in vitro. Importantly, those ablated primary T cells were activated cells. Meanwhile, naive T cells were spared by the BiKE treatment, supporting the crucial selectivity of PD-1 BiKE-directed cell depletion. Lastly, PD-1 BiKE is more effective than a conventional depleting antibody in the depletion of PD-1⁺ cells. The current work supports PD-1 BiKE is a selective, potent, and safe tool to deplete PD-1⁺ cells.

Objective:To explore the impact of self-disclosure on demoralization syndrome in patients with permanent enterostomy for colorectal cancer, so as to provide reference for clinical nursing interventions for those patients.Methods:From January to May 2023, convenience sampling was used to select 207 patients with permanent enterostomy for colocrctal cancer of the Wound Ostomy Clinic of Laoshan Campus of the Affiliated Hospital of Qingdao University as the research subjects. A survey was conducted on patients using the General Information Questionnaire, Distress Disclosure Index, Social Support Rating Scale, and the Demoralization Scale Mandarin Version.Results:Among 207 patients with permanent enterostomy for colorectal cancer, the scores of self-disclosure, social support, and demoralization syndrome were 35.00 (26.00, 47.00) , 32.00 (26.00, 39.00) , and 35.00 (23.00, 47.00) , respectively. A total of 128 patients (61.8%) were in moderate demoralization, and 37 patients (17.9%) were in severe demoralization. Multiple linear regression analysis showed that place of residence, self-care of stoma, self-disclosure, and social support were the influencing factors for demoralization syndrome in patients with permanent enterostomy for colorectal cancer ( P<0.05) . Conclusions:Patients with permanent enterostomy for colorectal cancer have a high overall score of demoralization syndrome, and a high proportion of patients with moderate to severe demoralization. Medical and nursing staff should focus on patients in remote rural areas and those with poor self-care abilities to stomas, develop targeted intervention measures to improve patients' negative emotions, enhance their self-disclosure, and pay attention to strengthening social support to relieve their demoralization syndrome, thereby improving their quality of life.

In May 2024, the World Health Organization (WHO) issued a position paper on the dengue vaccines, focusing on the newly licensed TAK-003 vaccine. WHO recommends that this vaccine be included in routine immunization schedules in areas of high-intensity dengue transmission, targeting children aged 6-16 years 1-2 years before the peak age of onset of dengue-related hospitalized cases, using a vaccination regimen with a two-dose interval of at least 3 months. Due to limited safety data, the vaccine is not recommended for specific populations such as pregnant women, lactating women, immunocompromised individuals, and symptomatic HIV-infected persons. The document also notes that the TAK-003 vaccine shows good safety and effectiveness in seropositive persons, but may not confer protection against DENV3 and DENV4 in seronegative vaccine recipients. The potential risk of severe dengue cannot be ruled out if seronegative persons are exposed to DENV3 and DENV4 based on currently available data. Additionally, the document mentions that the cost-effectiveness of the TAK-003 vaccine may vary with transmission intensity and age at vaccination, necessitating evaluation in different transmission settings. Currently, there is no data on the use of booster doses, therefore a booster dose is not recommended. Finally, the document notes that the TAK-003 vaccine can be given concurrently with yellow fever and hepatitis A vaccines, and that studies of concurrent vaccination with HPV vaccine are ongoing, which opens up more possibilities for future dengue vaccination strategies.

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

Objective:To explore the value of the aMAP risk score (age, male, albumin -bilirubin, and platelets) to predict early recurrence within one year after microwave ablation in patients with small hepatocellular carcinoma. Methods:This was a retrospective study that enrolled 142 patients diagnosed with hepatocellular carcinoma who were treated with microwave ablation in the Department of Hepatology Unit of Nanfang Hospital, Southern Medical University from July 2016 to July 2021. The cohort enrolled 121 male and 21 female patients, including 110 patients that were <60 years old. All the patients were followed-up after microwave ablation to evaluate residual tumor and recurrence of tumor by computed tomography or magnetic resonance imaging. The observation indices mainly included general data and imaging data of patients. Using the X-tile tools, patients were divided into two groups: a high aMAP score group and a low aMAP score group. Multivariate Cox regression analysis was conducted for comparison of independent risk factors.Results:Multivariate Cox regression showed that high aMAP score, maximum tumor diameter >20 mm, and high AFP were the independent risk factors of early recurrence (all P<0.05). Kaplan-Meier survival curves showed that the median recurrence-free survival was 25.5 months in the low aMAP score group and 6.1 months in the high aMAP score group ( P=0.001). Conclusions:The aMAP score could predict the early recurrence within 1 year of small hepatocellular carcinoma after microwave ablation. Patients with high aMAP score should undergo rigorous postoperative follow-up evaluations..

Objective:To investigate the impact of adding human menopausal gonadotropin (hMG) for in vitro fertilization-embryo transfer pregnancy outcomes in a standard population of non-advanced age with normal ovarian reserve function using a long follicular phase protocol.Methods:Clinical data of 489 patients with normal ovarian reserve function, who were admitted from January 2018 to January 2020 in the Affiliated Hospital of Guizhou Medical University and underwent in vitro fertilization for the first time with the long follicular phase protocol in fresh cycles, were retrospectively analyzed. The patients were divided into three groups according to whether or not to add urine-derived hMG and the timing of addition: non-addition group (group A), medium-term hMG group (group B1), whole course hMG group (group B2); the laboratory parameters of each group were observed, and the effect of ovulation induction drugs and pregnancy outcomes were compared.Results:The ages of B1 and B2 groups were significantly higher than that of group A ( P=0.019 and P=0.011). The basal FSH level of group B2 was significantly higher than those of group A and group B1 ( P<0.01 and P=0.006), and the basal FSH/LH ratio of group B2 was significantly higher than that of group B1 ( P=0.009). Antral follicle counts of group A and group B1 were significantly higher than that of group B2 ( P=0.007 and P=0.017). The superior embryo rate of group B2 [(47±27)%] was significantly higher than that of group A ( P=0.017). The embryo implantation rate of group B1 was significantly lower than those of group A and group B2 ( P=0.043 and P<0.01). The clinical pregnancy rate of group B2 [76.7% (155/202)] was significantly higher than those of group A ( P=0.039) and group B1 ( P<0.01). The live-birth rate of group B2 [67.3% (136/202)] was significantly higher than those of group A ( P=0.017) and group B1 ( P=0.001). Conclusions:For non-advanced aged patients with normal ovarian reserve function, the long protocol of follicular phase is suitable for those with relatively low ovarian reserve function. Adding hMG in the whole course of ovulation induction after gonadotropin-releasing hormone agonist reduction could improve the pregnancy outcomes by improving the quality of embryos.

Due to good mechanical properties and biocompatibility, tissue engineering scaffolds have become the vital method for repairing and regenerating articular cartilage defects. With the continuous development of tissue engineering technology, many scaffolds preparation and formation methods have been developed and tested in the past decade, however, the preparation of ideal regenerative scaffolds remain controversial. As load-bearing tissue inside the body joints, the matrix structure and cell composition of articular cartilage are hierarchical, and there are several smooth natural gradients from the cartilage surface to the subchondral bone layer, including cell phenotype and number, specific growth factors, matrix composition, fiber arrangement, mechanical properties, nutrient and oxygen consumption. Therefore, in the design of regenerative scaffolds, it is necessary to achieve these gradients to regenerate articular cartilage in situ. In recent studies, many new biomimetic gradient scaffolds have been used to simulate the natural gradient of articular cartilage. These scaffolds show different mechanical, physicochemical or biological gradients in the structure, and have achieved good repair effects. The related articles on tissue engineering for the treatment of articular cartilage defects were retrieved by searching databases with key wordsarticular cartilage injury, cartilage repair and gradient scaffolds. In this work,the structural, biochemical, biomechanical and nutrient metabolism gradients of natural articular cartilage were studied and summarized firstly. Then, the latest design and construction of articular cartilage gradient scaffolds were classified. Besides that, the material composition (such as hydrogels, nanomaterials, etc.) and the preparation process (such as electrospinning, 3D printing, etc.) of grandient scaffolds were further enhanced. Finally, the prospect and challenge of biomimetic gradient scaffolds in cartilage engineering are discussed, which provides a theoretical basis for the successful application of gradient scaffolds in clinical transformation.

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 speculate the effect of birth spacing on the pelvic floor type Ⅰ and Ⅱ fiber muscle strength of postpartum women with parities of two in different delivery modes.Methods:Totally 2 361 parturients who were investigated in Xuzhou Central Hospital from June 2016 to December 2020 were included in the questionnaire, clinical examination and pelvic floor surface electromyography assessment. According to the interval years between two parities and the pelvic floor typeⅠ and Ⅱ fiber muscle strength under different modes of delivery, curve fitting function equation was performed using curve regression method. The accuracy of the equation was verified by the receiver operating characteristic curve and the maximum area under the curve, and calculating the relative error rate.Results:A total of 2 357 parturients were included in the study and were divided into 4 groups based on delivery modes, women with both normal vaginal delivery were assigned to group A (589 cases); women with a first vaginal delivery and a second cesarean section were assigned to group B (480 cases); women with both cesarean deliveries were assigned to group C (1 273 cases); women with a first cesarean section and a second vaginal delivery were assigned to group D (15 cases). All of the curve fitting results were quadratic curves, and the appropriate interval years were selected when the muscle strength of type Ⅰ muscle fibers was>35 μV and that of type Ⅱ muscle fibers was>40 μV: 6-8 years in the group A, 5-10 years in the group B, and 1-11 years in the group C. The peak values of the quadratic curve were as follows: 7-8 years in the group A, 7-8 years in the group B, and 6 years in the group C. The maximum area under the curve of the function equations were all>0.6 (all P<0.05), the average relative error rate was 4.909%. Conclusions:The pelvic floor function of postpartum women with parities of two increases firstly and then decreases over time, showing a quadratic curve shape. In order to protect the pelvic floor function, the appropriate interval of birth spacing is 6-8 years.

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.