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*

In recent years,there has been a consensus regarding the enhancement of prognosis in patients with ad-vanced non-small cell lung cancer(NSCLC)through the utilization of immune checkpoint inhibitors(ICIs).Numerous clini-cal studies have also demonstrated the substantial value of immunotherapy for resectable NSCLC patients.Nevertheless,there remain controversies surrounding the exploration of immune combination strategies,treatment-related side effects,prognostic biomarkers,as well as other issues in the neoadjuvant therapy setting.Consequently,this article presents a comprehensive overview of the recent advancements in neoadjuvant immunotherapy for resectable NSCLC,stimulating fresh perspectives and delving into its merits and challenges in clinical application.

Large cell neuroendocrine carcinoma(LCNEC)of lung is a rare neuroendocrine carcinoma subtype with difficulty in early diagnosis and poor prognosis which is treated with standard strategies of small cell lung cancer and non-small cell lung cancer.In recent years,the precise types of LCNEC and its response to therapy have been identified by next-generation sequencing.Some researches have also found the correlation between different subtypes of LCNEC and the efficacy of chemotherapy regimens.However,there is no consensual agreement of its therapy.Recently,immune checkpoint inhibitors(ICIs)has provided a new option for LCNEC patients based on some retrospective research data and case reports.In this review,we aimed to summarize the epidemiological characteristics,standard therapy,the advances of molecular subtypes and clinical applications of ICIs of LCNEC,so as to provide optimal systemic clinical decision-making for LCNEC patients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

BACKGROUND: A prognostic nutritional index (PNI) developed by nutritional status and inflammation are closely associated with poor prognosis in malignant tumors. However, the predictive impact of PNI in patients with malignant pleural effusion (MPE) remains inconclusive. The study aimed to determine the predictive value of PNI in prognosis and spontaneous pleurodesis among patients with MPE. METHODS: The patients diagnosed with advanced non-small cell lung cancer (NSCLC) with MPE in West China Hospital between January 2015 and December 2022 were reviewed and allocated randomly to development set(60%) and validation set(40%). After collecting clinical data, peripheral blood inflammation indices and calculating systemic inflammation indices, the effects of PNI on prognosis and spontaneous pleurodesis have been evaluated by Cox proportional hazards models, Kaplan-Meier method and Nelson-Aalen cumulative risk curve. RESULTS: In total, 261 patients diagnosed NSCLC with MPE were selected (development set: n=157; validation set: n=104), of whom 58.2% were aged <65 years, 53.6% were male and 95.8% were diagnosed with adenocarcinoma. The dichotomous cut-off value for PNI was 44.1, respectively. Compared with lower PNI (PNI<44.1) cases, patients with higher PNI (PNI≥44.1) showed significantly longer overall survival (36.5 vs 24.3 mon, P=0.02) and higher incidence of spontaneous pleurodesis (P=0.009). According to the multivariate Cox analysis, higher PNI was associated with good prognosis and successful spontaneous pleurodesis (P<0.05). According to the results of Cox regression analysis, the PNI-prognosis and PNI-spontaneous pleurodesis models are determined, the receiver operating characteristic (ROC) curves are drawn, and the area under the curves (AUC) value of development set are 0.694 (95%CI: 0.620-0.776) and 0.673 (95%CI: 0.590-0.737). CONCLUSIONS PNI is a reliable biomarker of prognosis and spontaneous pleurodesis in patients with MPE. Attention to the patient's nutritional status and inflammation may improve the prognosis and efficacy of pleural effusion.
Humans ; Male ; Female ; Middle Aged ; Carcinoma, Non-Small-Cell Lung/mortality* ; Lung Neoplasms/mortality* ; Aged ; Prognosis ; Pleurodesis ; Pleural Effusion, Malignant/mortality* ; Nutrition Assessment ; Adult ; Nutritional Status

Central nervous system （CNS） is a sophisticated system subject to complex regulation， which dominates the high-level neural activities of the human body. Due to its complex physiological structure and refined regulatory mechanism covering a variety of diseases， CNS is the place where many chronic， refractory and rare diseases occur. Nerve cell is the basic unit of CNS， and its dysfunction and death is the root cause of CNS diseases. Ferroptosis is a new form of programmed cell death proposed in recent years， and has been proved to be closely related to the production and development of multiple CNS diseases. Traditional Chinese medicine （TCM）， including Chinese herbs， acupuncture and moxibustion， and massage， has shown unique advantages in the treatment of CNS diseases for a long time. A large number of studies have demonstrated that TCM participates in the regulation of CNS diseases via regulating ferroptosis and shows a good research prospect. This paper summarized the characteristics of ferroptosis and discussed the association between ferroptosis and CNS diseases in pathological mechanism. We also reviewed the regulation of various CNS diseases by different TCM interventions through ferroptosis， providing references for TCM to participate in the treatment of CNS diseases properly in the future.

Humans ; COVID-19 ; Epidemics ; Respiratory Tract Diseases ; Hospitalization

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Lung cancer is the malignancy with the highest mortality rate worldwide. Malignant pleural effusion (MPE) caused by advanced lung cancer severely affects the quality of life and prognosis of patients. Tumor-associated genetic testing is the basis for making precise treatment decisions. There are some risks of tissue biopsy, and it is difficult to sample repeatedly. Due to its non-invasive and can reflect the full profile of tumor gene characteristics, liquid biopsy is increasingly used in the diagnosis and treatment of lung cancer. Because of the extremely low DNA level of circulating tumor, the sensitivity and specificity of liquid biopsy based on blood samples are limited. Tumor cells is enriched in MPE. The detection of cell-free DNA, extracellular vesicles and microRNA in MPE will be helpful to the diagnose, treatment and assess prognosis of patients with lung cancer. This review aims to discuss the research progress of liquid biopsy based on MPE in the diagnosis and treatment of lung cancer patients.
.

Objective:To investigate the clinical effects of robot-assisted minimally invasive percutaneous pedicle screwing in the treatment of multi-segmental thoracolumbar burst fractures without neurological dysfunction.Methods:A retrospective analysis was conducted of the 24 patients who had been treated at Department of Orthopaedics, Hospital Affiliated to Inner Mongolia Medical University for multi-segmental thoracolumbar fractures from January 2019 to December 2020. They were randomly divided into a robot group ( n=12) in which the minimally invasive percutaneous pedicle screwing was assisted by a surgical robot and a manual group ( n=12) in which the minimally invasive percutaneous pedicle screwing was performed manually. There were 8 males and 4 females in the robot group, aged from 35 to 74 years; there were 7 males and 5 females in the manual group, aged from 36 to 69 years. The clinical effects were evaluated by comparing the 2 groups in terms of operation time, fluoroscopy frequency, fluoroscopy time, intra-operative needle adjustments, intra-operative blood loss, screwing accuracy, and visual analogue scale (VAS) scores, anterior vertebral height ratios and sagittal cobb angles at preoperation, postoperative 3 days and the last follow-up. Results:There was no statistically significant difference in the preoperative general data between the 2 groups, showing comparability ( P>0.05). A total of 128 screws were implanted in the robot group and 126 ones in the manual group. In the robotic group, operation time [(129.2±10.5) min], fluoroscopy frequency [(8.5±2.1) times], fluoroscopy time [(9.8±1.9) s], guide needle adjustments [(2.3±1.4) times], and intraoperative blood loss [(65.3±9.8) mL] were significantly less than those in the manual group [(153.8±18.1) min, (39.8±5.1) times, (43.9±4.8) s, (18.6±2.6) times and (96.8±10.9) mL] (all P<0.05). Regarding the screwing accuracy evaluated using CT scanning, the robot group was significantly higher (93.75%, 120/128) than the manual group (84.92%, 107/126) ( P<0.05). There was no significant difference between the 2 groups in VAS score, anterior vertebral height ratio or sagittal cobb angle at postoperative 3 days or the last follow-up ( P>0.05). The VAS scores, anterior vertebral height ratios and sagittal cobb angles at postoperative 3 days and the last follow-up were significantly improved than the preoperative values in all patients ( P<0.05). There was no supplementary surgery or screw loosening in either of the 2 groups. Conclusion:In the treatment of multi-segmental thoracolumbar fractures, robot-assisted percutaneous pedicle screwing can achieve satisfactory clinical effects, because, compared with traditional open surgery, it has exhibited advantages of less operation time, lower radiation exposure, less intraoperative blood loss, and higher screwing accuracy.