ObjectiveTo evaluate the effects and safety of the optimized new Shengmai Powder （优化新生脉散方） on exercise tolerance in patients with chronic heart failure （CHF） of qi deficiency， blood stasis， and fluid retention syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 78 CHF patients with qi deficiency， blood stasis， and fluid retention syndrome were recruited and randomly assigned to a treatment group （39 cases） and a control group （39 cases）. On the basis of conventional western medical therapy， patients in the treatment group additionally received the optimized new Shengmai Powder granules， while the control group was given an oral placebo of optimized new Shengmai Powder granules. Patients in both groups took 30.6 g each time， twice a day， mixed with water for administration， with a total treatment course of 4 weeks. The primary outcomes were 6-minute walk distance （6MWD） and peak oxygen uptake （Peak VO₂） measured by cardiopulmonary exercise testing. Secondary outcomes included New York Heart Association （NYHA） functional classification， B-type natriuretic peptide （BNP） levels， cardiac function indexes including left ventricular ejection fraction （LVEF）， left ventri-cular end-systolic diameter （LVESD） and left ventricular end-diastolic diameter （LVEDD）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） scores， and scores of four diagnostic information of traditional Chinese medicine （TCM）. All indicators were assessed once before and after treatment respectively. Safety indicators were evaluated， and adverse events during the trial were recorded. ResultsAll patients in both groups were included in the full ana-lysis set （FAS） and safety set （SS）. Compared with baseline， the 6MWD and Peak VO₂ of cardiopulmonary exercise test in the treatment group significantly increased after treatment， while the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information significantly decreased， and the NYHA cardiac function grade significantly improved （P＜0.01）. After treatment， the 6MWD and Peak VO₂ of cardiopulmonary exercise test， as well as their changes from baseline in the treatment group were higher than those in the control group； the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information in the treatment group were lower than those in the control group； and the improvement of NYHA cardiac function grade in the treatment group was superior to that in the control group （P＜0.01）. There was no statistically significant differences in all indicators after treatment in the control group （P＞0.05）. The incidence of adverse events was 5.1% （2/39） in the treatment group and 2.6% （1/39） in the control group， with no statistically significant difference between groups （P＞0.05）. ConclusionOn the basis of conventional western medicine treatment， the addition of the optimized new Shengmai Powder can further improve exercise tolerance， cardiac function and quality of life in patients with CHF of qi deficiency， blood stasis and fluid retention syndrome， and show good safety.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

Objective To investigate the effect of platelet lysate on mitochondrial function of astrocytes after spinal cord injury.Methods Astrocytoma cells SVGp12 were incubated with different concentrations of H2O2 (100 μmol/L,400 μmol/L,1000 μmol/L,2000 μmol/L),and the OD value was determined by CCK-8 assay. The H2O2 concentration with a cell inhibition rate of about 50％ was selected for follow-up experiments. The cells were incubated with different concentrations of platelet lysate (the volume ratios of platelet lysate to culture medium were 1∶10,1∶40,1∶80,1∶160 and 1∶320) for 24 hours,and the OD value was determined,thereby selecting the optimal concentration of platelet lysate based on the cell survival rate. SVGp12 cells were divided into the normal group (cultured normally without special treat-ment),the model group (incubated with 1000 μmol/L of H2O2 for 3 hours),and the treatment group (incubated with 1000 μmol/L of H2O2 for 3 hours and then treated with platelet lysate at a volume ratio of 1∶80). The mitochondrial function was evaluated by mitochondrial activity staining,mitochondrial membrane potential detection,and mitochondrial permeability transition pore detection. Results After incubating cells with 1000 μmol/L of H2O2 for 3 hours,the cell inhibition rate was 48％,and the OD value decreased significantly (P<0.01),confirming the successful establishment of a model of astrocytes with spinal cord injury. After treated with different concentrations of platelet lysate,the OD values and cell survival rate of the cells were higher than those in the model group (P<0.05). The concentration of platelet lysate (volume ratio of 1∶80) with cell viability of 20％ was selected for follow-up experiments. Platelet lysate could improve the morphology of injured astrocytes. The mitochondrial activity of the treatment group was significantly higher than that of the model group,and the mitochondrial activity of the model group was significantly lower than that of the normal group,with statistically significant differences (P<0.05). The mitochondrial membrane potential in the model group was lower than that in the normal group,and the mitochondrial membrane potential in the treatment group was higher than that in the model group,with statistically significant differences (P<0.01). The mitochondrial permeability in the model group was greater than that in the normal group,and the mitochondrial permeability in the treatment group was smaller than that in the model group,with statistically significant differences (P<0.01).Conclusion Platelet lysate can improve the survival rate of astrocytes after spinal cord injury,enhance the mitochondrial activity of cells,and improve the mitochondrial membrane potential and mitochondrial permeability transition pore opening.

Objective:To compare the efficacy of body posture combined with pharmacotherapy and pharmacotherapy alone in the treatment of chronic subdural hematoma(CSDH).Methods:Firstly, retrospective case series study was conducted. Thirty cases of CSDH that had received body posture combined with pharmacotherapy at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University from December 2016 to October 2020 were studied retrospectively. Twenty-seven patients were male, and 3 patients were female. The age of patients ( M(IQR)) was 66(16) years (range:28 to 84). Nineteen patients had unilateral hematoma, and 11 patients had bilateral hematoma. All patients received pharmacotherapy and body posture therapy that was to raise their lower limbs 20 to 30 cm with leg lift pad and get abdominal compressed with customized abdominal belt in supine position. Patients were required to maintain the body posture as much as possible, with the maximum to 16 to 18 hours per day. Patients with unilateral hematoma should tilt the head to the affected side and avoid tilting it to the opposite side. For patients with bilateral hematoma, there was no need for head lateralization. Patient were treated with oral dexamethasone and atorvastatin simultaneously. The preliminary efficacy of body posture combined with pharmacotherapy was determined by hematoma improvement rate which was analyzed by Clopper-Pearson method. Then, the multi-center, prospective, randomized controlled trial had carried out in 9 medical centers from August 2020 to November 2021. The stratified block randomization method was adopted. Patients were randomized in a ratio of 1∶1 to either receive pharmacotherapy alone(the control group) or body posture combined with pharmacotherapy(the experiment group) for 3 months and followed up for 6 months. Effective treatment was defined as complete absorption of hematoma, or the hematoma volume decreased by more than 10 ml and Markwalder grading scale score had improved by more than 1 point compared to the baseline. The efficacy rate and surgery conversion rate at 3 months and recurrence at 6 months were observed. Comparison between groups was performed with paired sample t test, Mann-Whitney U test, χ2 test, corrected χ2 test, or Fisher exact probability method. Logistic regression was used to compare the effective rate and operation rate between the two groups. Results:In the respective study, 30 patients completed follow-up 13 to 353 days after treatment. At the last follow-up, the incidence of almost complete absorption or significantly absorption of hematoma (hematoma volume was significantly reduced accompanied by symptom improvement) was 93.3%. The 95% CI for the incidence that analyzed by the Clopper-Pearson method was 77.9% to 99.2%. One hundred and six patients were enrolled in the multicenter study. Fifty-five patients underwent body posture combined with pharmacotherapy. The age was 74(17) years (range:26 to 92). Thirty-nine patients were males and 16 were females. Fifty-one patients underwent pharmacotherapy alone. The age was 69(12) years (range:48 to 84). Thirty-seven patients were males and 14 were females. The length of body posture recorded in diary card was (15.7±2.3) hours(range:7.6 to 19.3 hours). The efficacy rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 83.6% (46/55) and 56.9% (29/51), respectively at 3 months. The result of the logistic regression analysis showed that the efficacy of body posture combined with pharmacotherapy group was better than that of pharmacotherapy alone group ( OR=3.88,95% CI:1.57 to 9.58, P=0.003). Surgery rate in the body posture combined with pharmacotherapy group and pharmacotherapy alone group were 5.5% (3/55) and 21.6% (11/51) respectively. The result of Logistic regression showed that the pharmacotherapy alone group was more likely to be converted to surgery ( OR=0.21,95% CI:0.05 to 0.80, P=0.023). At the 6 months, no recurrence of cases was found in the body posture combined with pharmacotherapy group. However, the recurrence rate of pharmacotherapy alone group was 6.3% (3/48), there was no significant difference between the two groups ( P>0.05). Conclusion:The effect of body posture combined with pharmacotherapy for chronic subdural hematoma is better than that of pharmacotherapy alone.

Objective:To analyze the efficacy and safety of standard chemotherapy and immune checkpoint inhibitors (CI) combined with radiotherapy (RT) in driver-gene negative (wild-type) oligometastatic non-small cell lung cancer (NSCLC) patients with central nervous system involvement.Methods:In this multicenter retrospective cohort study, oligometastatic NSCLC patients receiving first-line chemo-immunotherapy-based therapy were analyzed. Between January 2017 and January 2023, a total of 98 eligible patients were enrolled from the National Cancer Center/Cancer Hospital (Beijing/Shenzhen) and Shanxi Province Cancer Hospital. All participants were divided into chemo-immunotherapy (CI) group (28.6%, n=28) and chemo-immuno-radiotherapy (CIR) group (71.4%, n=70) according to whether receiving radiotherapy. Baseline characteristics were well-balanced between two groups, with no statistically significant differences (all P>0.05). The primary endpoint of the study was overall survival (OS), while progression-free survival (PFS) was designated as a key secondary endpoint. Qualitative data were compared by Chi-square test. Survival analysis was conducted using Kaplan-Meier method, and prognostic analysis was performed by multivariate Cox regression models. Results:The median PFS in the CIR and CI groups was 21.8 and 11.5 months, respectively, and the difference was not statistically significant ( P=0.211). The median OS in the CIR group was significantly better ( P=0.036) than 25.3 months in the CI group. The median OS in the CIR group was not reached. The 2-year local regional control rates for the whole brain radiotherapy patients, stereotactic radiotherapy / stereotactic radiosurgery patients and CI groups were 33.3% ,100% and 83.4%, respectively. Multivariate analysis showed that brain radiotherapy was an independent protective factor for OS in patients with oligometastatic brain metastases at baseline ( HR=0.47, 95% CI=0.22-0.99, P=0.047). Subgroup analysis revealed that patients with 1-3 metastatic lesions benefited from radiotherapy (PFS: HR=0.47, 95% CI=0.22-1.03, P=0.060; OS: HR=0.34, 95% CI=0.12-0.98, P=0.046). Conclusions:For central nervous system involved oligometastatic NSCLC patients, the integration of chemo-immunotherapy with radiotherapy is well tolerated and can improve the efficacy, particularly among those with a limited number of metastatic lesions.

Objective To assess the effectiveness of the Gasdermin D C-terminal fragment(GSDMD-CT)as a novel plasma biomarker for the clinical diagnosis of sepsis.Methods Between July 2021 and November 2024,245 patients from Tangshan Gongren Hospital were enrolled in this study.In accordance with the diagnostic criteria for sepsis and the systemic inflammatory response syndrome(SIRS),patient samples were classified into the sepsis group and the SIRS group.Meanwhile,healthy individuals were selected as the healthy control(HC)group.Sepsis patients were further categorized into the Gram-positive bacterial group,the Gram-negative bacterial group,and the fungal group based on the type of pathogen infection.The levels of GSDMD-CT,C-reactive protein(CRP),and procalcitonin(PCT)were measured in all subjects.Nonparametric tests were employed to compare the differences in various indices among different groups.The diagnostic value of GSDMD-CT in sepsis was evalu-ated by constructing the receiver operating characteristic(ROC)curve.Spearman's correlation analysis was used to examine the relationships among GSDMD-CT,CRP,and PCT.Results The plasma GSDMD-CT levels in the sepsis group 23.02(16.71,33.01)pg/mL and in the SIRS group 16.52(11.26,22.22)pg/mL were significantly higher than those in the healthy control group 7.02(4.42,11.43)pg/mL(U=-10.175,-7.890,P<0.001).Moreover,the plasma GSDMD-CT levels in the sepsis group were significantly higher than those in the SIRS group(U=-2.941,P<0.05).In the Gram-positive bacterial group,the Gram-negative bacterial group,and the fungal group,the GSDMD-CT levels were 23.01(17.16,27.51)pg/mL,23.41(16.78,35.50)pg/mL,and 16.29(14.53,56.27)pg/mL,respectively.When compared with the healthy control group,the GSDMD-CT levels in these three groups were all significantly higher(P<0.05).However,there were no significant differences in GSDMD-CT levels among these three groups(P>0.05).The area under the curve(AUC)of plasma GSDMD-CT for diagnosing sepsis was 0.881(95%confidence interval:0.833～0.929),with a Youden index(YI)of 0.695,a sensitivity of 85.0%,and a specificity of 84.5%.Spearman correlation analysis indicated a weak correlation between GSDMD-CT and C-reactive protein(CRP)(r=0.32,P<0.001)and a positive correlation between GSDMD-CT and procalci-tonin(PCT)(r=0.65,P<0.001).Conclusion GSDMD-CT exhibits significant clinical value in the diagnosis of sepsis and holds great potential as a biomarker in the diagnostic process of sepsis.

Objective:To explore the short-term clinical effects of deep cervical lymph node-venous anastomosis in the treatment of Alzheimer’s disease (AD).Methods:A prospective exploratory study was conducted on the treatment of AD patients using the cervical deep lymph node-venous anastomosis technique in Scar and Wound Treatment Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, from September to October 2024. The patients underwent high-frequency ultrasound to locate deep cervical lymph nodes and the external jugular vein. Under general anesthesia, bilateral deep cervical lymph node-venous anastomoses were performed. Indocyanine green (ICG) lymphography was conducted via subcutaneous injection behind the ear to visualize lymph nodes in levels Ⅱ and Ⅲ. After making a skin incision along the posterior margin of the sternocleidomastoid muscle, the external jugular vein, internal jugular veins, and associated lymph nodes were exposed. Adjacent veins were selected for anastomosis of lymph node. Using microsurgical techniques, end-to-side or end-to-end anastomosis was completed for lymph nodes in levels Ⅱ and Ⅲ. Preoperative assessments included the mini-mental state examination (MMSE, a higher score indicates better cognitive function), Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog, a higher score indicates greater impairment of cognitive function), Alzheimer’s disease cooperative study scale for activities of daily living (ADCS-ADL, a higher score indicates better ability to perform daily activity), and neuropsychiatric inventory (NPI, a higher score indicates more severe behavioral and emotional symptom). Postoperative follow-up included the same scales to observe changes in cognitive function, activities of daily living, and emotional communication.Results:Four patients (1 male, 3 females, aged 58-79 years) with AD were included. All were diagnosed based on cerebrospinal fluid biomarkers. All patients successfully underwent bilateral deep cervical lymph node-venous anastomoses. On average, 4.3 (2-7 per person) anastomoses were performed per patient. Surgical procedures lasted an average of 6.5 h (5.5-8.5 h) with minimal blood loss (less than 50 ml). Patients resumed normal activity within 6 hours postoperatively and were discharged after an average of 4.1 d (3.5-5.0 d). Postoperative complications included one case each of aspiration pneumonia, lower limb venous thrombosis, and transient delirium, all of whom resolved without long-term effects. Clinical symptoms, including memory decline, mood swings, and anxiety, showed varying degrees of improvement. Patients reported enhanced quality of life, emotional stability, and social engagement, confirming the procedure’s safety and potential cognitive benefits. At one month postoperatively, the MMSE scores of the four patients increased by an average of 0.8 points compared to preoperative levels. Additionally, the two patients who completed the ADAS-Cog assessments showed a decrease in their scores (reduced by 1.0 points and 11.3 points, respectively, compared to preoperative scores), indicating a certain degree of improvement in cognitive function during this period. The ADCS-ADL and NPI scores of four patients varied significantly, without showing any clear pattern.Conclusion:Lymphovenous anastomosis of the deep cervical lymph node-venous anastomosis may provide a new surgical intervention approach for AD, but further large-scale studies and long-term follow-up are needed to validate its safety and effectiveness.