This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

Objective: To investigate associations of suicidal ideation with clinical features, inflammatory markers, and thyroid hormones in patients with schizophrenia. Methods: The subjects of this study were 203 schizophrenic patients, grouped on the basis of suicidal ideation. Clinical characteristics were assessed using multiple scales. Neutrophil to lymphocyte ratio(NLR), platelet to lymphocyte ratio(PLR), monocyte to lymphocyte ratio(MLR) and thyroid hormones were also detected. SPSS 23.0 was used for statistical analyses. Results : The prevalence of suicidal ideation was 21.7% in patients with schizophrenia. Logistic stepwise regression analyses showed that Calgary depression scale(CDSS) total score(OR=1.490, 95%CI=1.287-1.724,P<0.001), insomnia severity index scale(ISI) total score(OR=1.096, 95%CI=1.011-1.187,P=0.025), modified overt aggression scale(MOAS) total score(OR=1.111, 95%CI=1.016-1.215,P=0.021), MLR(Ln)(OR=15.123, 95%CI=3.868-59.125,P<0.001), and triiodothyronine(T3)(OR=0.037, 95%CI=0.003-0.388,P=0.006) were the independent influences of suicidal ideation. Additionally, receiver operating characteristic(ROC) curve analyses revealed that the five-item combination of CDSS total score, ISI total score, MOAS total score, MLR(Ln), and T3(AUC=0.908, 95%CI=0.867-0.949,P<0.001) had better ability to identify suicidal ideation. Conclusion The risk of suicidal ideation is relatively high in patients with schizophrenia, and there may be stronger associations between suicidal ideation and depression, insomnia, aggression, MLR, and T3.

Traumatic brain injury(TBI)is a serious condition characterized by high rates of mortality and disability.Deaths caused by severe TBI usually occur within the first few hours after the injury.Timely and effective management of TBI during pre-hospital and emergency treatment phases is crucial for improving patients'prognosis.To address this issue,the Emergency Physicians Branch of the Chinese Medical Doctor Association,the Emergency Medicine Professional Committee of the People's Liberation Army,the Beijing Emergency Medicine Society,and the Chinese Emergency Medicine Specialist Association have jointly selected national experts in emergency medicine and neurosurgery to formulate the"Chinese Expert Consensus on the Pre-hospital and Emergency Diagnosis and Treatment of Adult Traumatic Brain Injury".This consensus consists of two parts focusing on pre-hospital and emergency diagnosis and treatment of TBI,with 24 recommendations put forward to guide relevant clinical practices in pre-hospital and emergency management.

Objective:To investigate the effects of short-term olfactory training and visual stimulation on olfactory recognition function and quality of life in patients following functional endoscopic sinus surgery (FESS).Methods:A total of 80 patients who underwent FESS in the Department of Otorhinolaryngology Head and Neck Surgery at the Affiliated Hospital of Xuzhou Medical University between December 2023 and February 2024 were enrolled in this study. The cohort comprised 67 males and 13 females, aged from 17 to 75 years. Participants were randomly allocated to either a control group ( n=40) or an experimental group ( n=40). The participants in control group received routine postoperative management, including nasal irrigation, oral antibiotics and glucocorticoids, topical budesonide nasal spray, and hypertonic saline solution for 12 weeks. In addition to the standard care, the participants in experimental group underwent olfactory-visual stimulation training starting 24 hours postoperatively, lasting for 2 weeks. The olfactory identification test (OIT), visual analogue scale (VAS) for olfaction and Questionnaire of Olfactory Disorders of Life (QOD-QoL, hereafter referred to as QOD) were administered preoperatively. Follow-up assessments were performed 2 weeks and 3 months postoperatively, with the same tests repeated. Data were analyzed using SPSS 27.0 and GraphPad Prism 7 statistical software. Results:There was no significant difference in preoperative OIT, VAS, and QOD scores between the two groups. The olfactory recognition function of some patients was improved after removing the packing material 24 hours after FESS surgery. The OIT scores of 2 weeks post-surgery were significantly higher than preoperative values in both groups (the experimental group Z=-4.73, P<0.001; the control group Z=-4.73, P<0.001). Participants in both groups showed improvements in olfactory VAS and QOD scores (experimental group Z value was -2.88 and -5.45, P<0.01 and<0.001, respectively; the control group Z value was -4.42 and -5.50, respectively, both P<0.001). However, there was no significant difference in the VAS score between the two groups ( Z=-0.68, P=0.499). The paticipants in experimental group showed greater improvement in OIT and greater reduction in QOD scores compared to the control group ( Z=-2.19, P=0.029; Z=-2.99, P=0.003). There was no significant difference in the decrease of olfactory VAS between the two groups ( Z=-0.02, P=0.988). There were no statistically significant differences of all patients in VAS, OIT and QOD scores at 2 weeks and 3 months after surgery (experimental group Z value was -0.91, -0.90 and -1.43, respectively, all P>0.05; control group Z value was -1.21, -0.84 and -0.91, respectively, all P>0.05). At 3 months post-surgery, the OIT scores in the experimental group were higher, the QOD scores were lower than those in the control group ( Z=-2.89, P=0.004; Z=-2.87, P=0.004). Conclusion:Short-term olfactory-visual stimulation training in the early postoperative period of FESS significantly improves the olfactory recognition function and enhances the quality of life of patients.

Objective:To investigate the effects of ascites grading and the application of non-selective beta-blockers (NSBBs) on the 1-year prognosis of acute-on-chronic liver failure (ACLF).Methods:1 386 ascitic cases with ACLF were graded and followed up for one year. The 1-year prognostic effect of ascites grade and NSBBs was analyzed on ACLF by the Kaplan Meier Log-rank test, Cox stepwise regression, and multivariate regression.The t-test, Mann-Whitney U, or Kruskal-Wallis test were used for intergroup comparison of measurement data. The χ2 test was used for intergroup comparison of numerical data. Results:The incidence rate of ascites at admission was 77.56% in 1 386 ACLF cases. The Log-rank (Mantel-Cox) of the 1-year survival curve test for 1 386 ACLF patients with ascites grade was 21.384, P<0.01. Multivariate regression and Cox stepwise regression analysis showed that ascites grade, age, gastrointestinal bleeding, pulmonary infection, acute kidney injury, prothrombin activity (PTA), urea, MELD-Na score, and the use of NSBBs were closely related to the 1-year prognosis of ACLF. The log rank (Mantel-Cox) of NSBBs treatment in the grade 2/3 ascites group was 6.113, P=0.013, and the difference was statistically significant, suggesting that NSBBs treatment can help improve the 1-year survival rate in ACLF patients with grade 2 and 3 ascites. Conclusions:Ascites grading and the use of NSBBs affect the prognostic factor of ACLF at one year. NSBBs may be beneficial for the long-term prognosis of ACLF, and treatment can be continued in patients who have already received NSBBs prior to the onset of ACLF.

Objective To translate Evidence-Informed Decision-Making Competence Measure for Chinese nurses and test its validity and reliability.Methods A research group was set up to use the Brislin translation model to translate the original scale into Chinese,and the back translation,cross-cultural adaptation,pre-experiment and cognitive interview were conducted to finally form the Chinese version of the Evidence-Informed Decision-Making Competence Measure for nurses.A total of 1 247 nurses from 7 tertiary A hospitals in Beijing,Hubei,Hunan and Xinjiang were selected by convenience sampling method in April 2024 to test its reliability and validity.Results 1 026 effective question-naires were collected,with an effective recovery rate of 82.28％.The Chinese version of the Evidence-Informed Decision-Making Competence Measure included 25 items,including knowledge/skill,attitude and behavior.A total of 3 common factors were extracted from exploratory factor analysis,and the cumulative variance contribution rate was 91.725％.The content validity index at the item level was 0.83-1.00;the content validity index at the scale level was 0.988;the calibration association validity was 0.496.The Cronbach's α coefficient of the whole scale was 0.992;the half-point reliability was 0.930;the retest reliability was 0.927.Conclusion The Chinese version of Evidence-Informed Decision-Making Competence Measure for nurses has good reliability and validity,and it can be used to evaluate the evidence-informed decision-making competence of Chinese nurses,provide references for promoting evidence-based nursing practice and evidence-informed decision-making.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Objective:To investigate the anti-tumor effect of the Histone Deacetylase 6 (HDAC6) inhibitor ACY-738 and its underlying mechanisms in Diffuse Large B-cell Lymphoma (DLBCL) .Methods:The expression of HDAC6 in various tumors and DLBCL was analyzed using bioinformatics. DLBCL cells were treated with different concentrations of ACY-738. Cell viability, DNA synthesis, and clone formation were assessed by CCK-8 assay, EdU assay, and soft agar assay, respectively. Intracellular reactive oxygen species (ROS) levels were detected by fluorescence microscopy. Morphological changes in cells were observed using transmission electron microscopy (TEM). Mitochondrial ROS levels and apoptosis were measured by flow cytometry. The expression levels of apoptosis-related and autophagy-related proteins were detected by Western blotting.Results:HDAC6 was highly expressed in DLBCL ( P<0.05). ACY-738 inhibited the proliferation, DNA synthesis, and colony formation of DLBCL cells in a dose-dependent manner ( P<0.05). Treatment with ACY-738 increased intracellular and mitochondrial ROS levels in DLBCL cells in a dose-dependent manner ( P<0.05). TEM revealed that after ACY-738 treatment, mitochondria in cells were swollen and ruptured, mitochondrial cristae were reduced or absent, autolysosomes appeared, and features characteristic of apoptosis were observed. Western blotting showed that after ACY-738 treatment, the expression of the anti-apoptotic protein BCL-2 was downregulated, while the expression of Cleaved-PARP, Cleaved caspase-3, and BAX was upregulated ( P<0.05). The expression of autophagy-related proteins Atg7, Atg3, LC3B, and P62 was downregulated, and the expression of acetylated P53 protein was upregulated ( P<0.05) . Conclusion:The HDAC6 inhibitor ACY-738 induces mitochondria-dependent apoptosis and autophagy in DLBCL cells by acetylating P53, thereby inhibiting DLBCL cell proliferation.

Objective:To analyze the clinical efficacy and learning curve of robotic-assisted Warshaw procedure using the da Vinci system.Methods:Clinical data of 91 consecutive patients with pancreatic body and tail lesions undergoing robotic-assisted Warshaw procedure at Qingdao University Affiliated Hospital from October 2021 to April 2023 were retrospectively analyzed, including 21 males and 70 females, aged (50.2±14.3) years. Patient characteristics, operative time, and intraoperative blood loss were recorded. The learning curve was constructed using cumulative sum (CUSUM) analysis, with case number on the x-axis and CUSUM values on the y-axis. Linear fitting was performed, and the model with the highest determination coefficient was selected as the optimal fitting model. The learning process was divided into two phases based on the inflection point of the CUSUM learning curve: the learning phase and the proficiency phase. Perioperative outcomes were compared between these two phases.Results:All 91 procedures were successfully completed using the da Vinci robotic system with R0 resection margins. There were no perioperative mortalities or reoperations due to postoperative splenic infarction. The operative time was (227.84±76.68) min. The optimal fitting equation for the CUSUM learning curve was: CUSUM=0.005 640X 3-1.501X 2+ 92.59X-183.1. The CUSUM learning curve showed an inflection point at case 39, dividing the learning process into the learning phase (cases 1-39) and proficiency phase (cases 40-91). Compared to the learning phase, the proficiency phase demonstrated significantly shorter operative time [(203.0±75.6) min vs. (260.9±65.5) min], less intraoperative blood loss [50.0 (20.0, 50.0) ml vs. 100.0 (50.0, 100.0) ml], and reduced postoperative drainage duration [(8.7±2.4) d vs. (10.8±3.2) d] (all P<0.05). Conclusion:The robotic-assisted Warshaw procedure feasible for patients with pancreatic body and tail lesions. Surgeons require approximately 39 cases to complete the learning curve and achieve proficiency in this procedure.

Objectives:To explore the efficacy of robotic-assisted retroperitoneal benign tumor resection and to analyze its learning curve.Methods:This is a retrospective case series study. The data of patients who underwent robotic-assisted retroperitoneal benign tumor resection from August 2015 to February 2023 at the Department of Retroperitoneal Tumor Surgery was analyzed retrospectively. There were 24 males and 45 females, with an age of (46.3±10.6) years (range: 19 to 76 years). The perioperative data, postoperative pathological results, and follow-up data were recorded. The cumulative sum (CUSUM) method was used to analyze the robotic system setup time and operative time to plot the learning curve. A linear regression model was applied to determine the best-fit curve, selecting the model with the highest R2 value. Based on the vertex of the learning curve for surgical time, the patients were divided into a learning group and a mastery group. The general data and perioperative conditions of the two groups were compared. Independent sample t-tests, Mann-Whitney U tests, and χ2 tests were used for comparisons. Results:All 69 patients successfully completed the surgery without intraoperative complications. The diameter of tumors was (49.7±18.6) mm (range: 16 to 131 mm). The setup time for the robotic surgical system was (35.3±9.8) minutes (range: 20 to 61 minutes); the surgical time was (169.2±36.5) minutes (range: 70 to 305 minutes); intraoperative blood loss ( M(IQR)) was 10.0 (15.0) ml (range: 2.0 to 200.0 ml). The tumors in 32 patients (46.4%) were adherent to major blood vessels. All patients were discharged without complications. The follow-up period lasted until February 2024, and no patients required reoperation, readmission, or died due to retroperitoneal benign tumors. There were no severe long-term complications, and no radiological evidence of tumor recurrence was found. The best-fit equation for the learning curve based on surgical time was CUSUM=0.010X3-1.648X2-68.573X-61.091, and the best-fit equation for the learning curve based on robotic system setup time was CUSUM=0.0018X3-0.285X2+10.460X+57.541 (where X represents the number of surgeries). The R2 values of 2 learning curve models were 0.953 and 0.957, respectively, and the fit model tests had P<0.05. The inflection point of the learning curve based on surgical time was the 28th case, which is considered the minimum number of surgeries required to achieve proficiency in robotic-assisted retroperitoneal benign tumor resection. Based on this, the patients were divided into a learning group (cases 1 to 28) and a mastery group (cases 29 to 69). The surgical time for the learning group was significantly longer than that of the mastery group ((194.7±30.0) minutes vs. (151.9±31.4) minutes, t=4.126, P<0.01). No statistically significant differences were found for other parameters (all P>0.05). Conclusions:Robotic-assisted retroperitoneal benign tumor resection is feasible. The minimum number of surgeries required to achieve proficiency in overcoming the learning curve is about 28 cases.