OBJECTIVE To investigate the effects of calcitriol on sepsis-induced immunosuppression and its potential mechanism. METHODS A sepsis-induced immunosuppression mice model was established using cecal ligation and puncture （CLP）. The 7-day survival rate， serum levels of tumor necrosis factor- α （TNF- α）， interleukin-6 （IL-6）， and IL-1β were determined in sham operation group， CLP group and calcitriol group （1 μg/kg）； the morphological changes of lung tissue in mice were observed. Lipopolysaccharide （LPS） tolerance macrophage models （representing sepsis-induced immunosuppression） were established using mice macrophage cell line RAW264.7 cells. The levels of TNF-α and IL-6 in cell supernatants as well as mRNA expressions of IL-1β， nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）， IL-18 and caspase-1 were assessed in culture medium group， LPS group， LPS tolerance group， and calcitriol （5 μmol/L） group. The following parameters were measured： propidium iodide （PI）-positive cell ratio， caspase-1 activity， lactate dehydrogenase （LDH） release， and Ca2+ levels. RESULTS Compared with CLP group， 7-day survival rate and serum levels of TNF-α， IL-6 and IL-1β were increased significantly in calcitriol group （P＜0.05）. Additionally， pulmonary tissue damage was markedly attenuated in calcitriol group. Compared with LPS tolerance group， the levels of TNF-α and IL-6 in cell supernatants， mRNA expressions of IL- 1β， NLRP3， IL-18 and caspase-1， PI-positive cell ratio， caspase-1 activity， LDH release， and Ca2+ levels were all increased significantly in calcitriol group （P＜0.05）. CONCLUSIONS Calcitriol can reverse sepsis-induced immunosuppression， and the mechanism of action may be E-mail：yarfwy@163.com achieved by the binding of calcitriol to vitamin D receptor，which promotes the release of Ca2+ from the endoplasmic reticulum， thereby driving the NLRP3/caspase-1-mediated pyroptosis pathway.

BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Tacrolimus is a commonly used medication for the treatment of nephrotic syndrome.Due to its narrow therapeutic window and significant pharmacokinetic differences among individuals,therapeutic drug monitoring is required during its clinical use.In the process of therapeutic drug monitoring,machine learning-based personalized dosing prediction models for tacrolimus can excavate medication patterns from a large amount of clinical data,assist in clinical decision-making,and achieve individualized precise medication.Machine learning models,the application progress of machine learning in personalized administration of tacrolimus for patients with nephrotic syndrome,modeling points of machine learning prediction models,and the limitations of current prediction models were reviewed in this paper,which could provide references for future research in this field.

Digital pulse diagnosis technology based on pulse chart parameters is one of the important achievements of the modernization and intelligent development of TCM diagnosis.Pulse diagnosis instrument collects pulse signals for feature extraction and analysis,which promotes the objectification and digital progress of TCM pulse diagnosis.This article discussed the research and application progress of the digital pulse diagnosis technology from four aspects:sensor types and research achievements of pulse diagnosis instrument,the application of pulse signals analysis method,research and analysis methods for multi-source signal fusion sensors,and the correlation between pulse parameters and cardiovascular disease,so as to provide new research ideas and methods for the further development of digital pulse diagnosis technology.

The Health-Related Quality of Life (HRQoL) pertains to patients' subjective contentment concerning their physical, psychological, and social well-being throughout disease treatments. Predominantly employed HRQoL metrics in spinal metastases comprise the 36-item Short-Form Health Survey (SF-36), EuroQoL Five Dimensions Questionnaire (EQ-5D), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Functional Assessment of Cancer Therapy-General (FACT-G). In clinical applications, due to their broad application and diverse disease types, combined with the lack of specificity in the scale content and the prolixity of their questionnaires, these tools often fail to capture the nuanced experiences of patients, thereby compromising the reliability and validity of the results. The Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ), developed by the Spine Oncology Study Group, offers a tailored metric for spinal metastases, encapsulating both specificity and inclusivity. Its proven robust reliability and validity make it invaluable for decision-making and therapeutic efficacy appraisals. The Patient-Reported Outcome Measurement Information System (PROMIS), a novel metric suitable across many medical disciplines, facilitates cross-sector data acquisition, substantially augmenting the precision, sensitivity, and credibilityof assessments, and is pivotal in clinical investigations and interventions. As it continually evolves, PROMIS consistently outperforms traditional metrics in evaluative capacities, exhibiting impressive and consistent proficiency in prognostications, preoperative assessments, and therapeutic outcome evaluations within the spinal metastasis domain. Presently, Chinese research on the HRQoL of spinal metastasis patients remains scant, and choosing an apt, precise, and dependable metric holds significant clinical relevance. Drawing upon extant scholarly publications, this review concluded the current global HRQoL tools for spinal metastases, aiming to furnish insights for the clinical management and research pertaining to spinal metastases.

OBJECTIVE To investigate the eff ects of hypoalbuminemia and human albumin supplementation on patients with acute kidney injury （AKI）after off-pump coronary artery bypass grafting （OPCABG）. METHODS From December 2018 to January 2020，clinical information of 484 patients with coronary atherosclerotic heart disease who underwent selective OPCABG in Tianjin Chest Hospital were analyzed retrospectively. The basic data ，American Society of Anesthesiologists （ASA）grading，the number of coronary artery bypass grafting ，amount of intraoperative bleeding ，use of artificial colloid ，minimum value of hemoglobin within 7 days after operation ，hypoalbuminemia occurred after operation ，monitoring time in postoperative intensive care unit ，drainage volume of thoracic catheterization ，perioperative blood transfusion ，amount of human albumin after operation were summarized. All patients were divided into non-AKI group （414 cases）and AKI group （70 cases）according to the occurrence of AKI. The differences of the above indexes between the two groups were compared. Multiple Logistic regression analysis was performed to analyze the risk factor of AKI when selecting the indexes with P＜0.1. According to whether hypoalbuminemia occurred after operation ，all patients were divided into normal protein group （347 cases）and hypoalbuminemia group （137 cases）. Hierarchical analysis was carried out to explore the correlation between human albumin supplementation and AKI. RESULTS The results of multiple Logistic regression analysis showed that there was no significant effect on AKI in postoperative hypoalbuminemia （P＞0.05），but there were significant effect in body mass index and the dosage of postoperative human serum albumin （P＜0.05）. The risk of AKI would increase by 12.7％ every time the body mass index increases by 1 unit；the risk of AKI increased by 17.3％ for every 10 g increase in the dosage of human albumin. Stratified analysis showed that the risk of AKI would increased by 26.9％ for every 10 g increase in postoperative human albumin supplementation in normal protein group and 14.0％ for every 10 g increase in postoperative human albumin supplementation in hypoalbuminemia group. CONCLUSIONS Hypoalbuminemia is not a risk factor fo r the development of AKI after OPCABG ，but human albumin supplementation is a risk factor for AKI after OPCABG.

Objective:To review the experience of closure of the left-main-bronchial stump fistula using endoscopic liner cutter staplers through the right thoracic approach and I stage or staged treatment for the left pyothorax.Methods:6 patients with the left-main-bronchial stump fistula after left pneumonectomy combined with pyothorax were treated by closing the left-main-bronchial stump using endoscopic liner cutter staplers through the right thoracic approach, and pleura was used to cover the distal and proximal incisional margin of the stump respectively. The thoracic T-tube drainage was used in the I stage or staged treatment for the left pyothorax.Results:All patients were survived without recurrence of the bronchopleural fistula. 4 patients were observed to have no recurrence of pyothorax when 1 patient had recurrence of pyothorax and was treated with intermittent T-tube drainage.1 patient operated with left-thoracic fenestration in the past was treated with drainage waiting for secondary operation.Conclusion:The right thoracic approach seemed to be a safer and more effective method than the transsternal transpericardial approach in cases with the left-main-bronchial stump fistula combined with pyothorax. The use of endoscopic liner cutter staplers reduced the risk of bleeding, infection and recurrence of fistula. The T-tube drainage in the I stage or staged treatment for the left pyothorax was considered to be an easier way for treatment.