Objective To investigate the effect of a three-tier delirium care management process in patients with acute stroke in neurology intensive care unit(NICU).Methods A total of 50 patients with acute stroke admitted to the NICU of the Fourth Hospital of Changsha from May to September 2021 were assigned to the control group.The patients in the control group received routine NICU nursing care to prevent delirium.Another 50 patients with acute stroke admitted to the NICU from December 2021 to April 2022 were assigned to the trial group.They were managed with the three-tier delirium nursing management process on top of the routine NICU nursing care for the control group.The incidence of ICU delirium(DICU),duration of DICU,length of stay in NICU and the incidence of delirium-related adverse events were compared between the two groups.The degree of delirium and cognitive function before and after the intervention were compared between the two groups as well.Results The trial group had significantly shorter duration of DICU and NICU stay(both P<0.05)and lower incidence rate of delirium-related adverse events(P<0.05)compared to the control group.After the intervention,the trial group showed significantly lower scores on the intensive care delirium screening checklist(ICDSC)and significantly higher scores of cognitive function compared to those of the control group(both P<0.05).Conclusion The three-tier delirium nursing management process can lower the occurrence of delirium in NICU patients with acute stroke,shorten the NICU stay,reduce the safety risk in nursing,and improve the cognitive function.

Objective To explore the clinical efficacy and safety of one-stage posterior lesion removal and internal spinal fixation in patients with lumbar Brucellosis spondylitis.Methods The clinical data of 24 patients admitted from October 2017 to October 2022 were retrospectively analyzed,2 patients were lost to follow-up at 10 months after surgery,at the final 22 cases were included in the study,including 13 males and 9 females with an average age of(52.00±6.89)years old,were treated with one-stage posterior lesion removal and internal spinal fixation.The operation time,intraoperative bleeding,follow-up time,ery-throcyte sedimentation rate(ESR)and C-reactive protein(CRP)before and after operation were recorded.The pain visual ana-logue scale(VAS),Oswestry disability index(ODI),the Japanese Orthopaedic Association(JOA)score for neurofunction,American Spinal Injury Association(ASIA)spinal cord injury grade and modified MacNab criteria were ussed to evaluate the efficacy.Results All patients were followed up from 12 to 30 months with an average of(17.41±4.45)months.The operation time was 70 to 155 min with an average of(1 16.59±24.32)min;the intraoperative bleeding volume was 120 to 520 ml with an average of(275.00±97.53)ml.CRP and ESR levels decreased more significantly at 1 week and at the final follow-up than pre-operative levels(P＜0.05).VAS,JOA score and ODI at 1 week and at the latest follow-up were more significantly improved than preoperative results(P＜0.05).There was no significant difference between ASIA preoperative and 1 week after operation(P＞0.05),and a significant difference between preoperative and last follow-up(P＜0.05).In the final follow-up,21 patients had ex-cellent efficacy,1 patient had fair,and there was no recurrence during the follow-up.Conclusion One-stage transpedicular le-sion removal and internal spinal fixation,with few incisions and short operation time,helps the recovery of neurological func-tion,and the prognosis meets the clinical requirements,which can effectively control Brucella spondylitis.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous system. Compared with patients with other cancers, glioma patients often suffer from increased levels of psychological stress, such as anxiety and fear. Chronic stress (CS) is thought to impact glioma profoundly. However, because of the complex mechanisms underlying CS and variability in individual tolerance, the role of CS in glioma remains unclear. This review suggests a new proposal to redivide the stress system into two parts. Neuronal activity is dominant upstream. Stress-signaling molecules produced by the neuroendocrine system are dominant downstream. We discuss the underlying molecular mechanisms by which CS impacts glioma. Potential pharmacological treatments are also summarized from the therapeutic perspective of CS.

Sucrose synthase plays a crucial role in the plant sugar metabolism pathway by catalyzing the production of uridine diphosphate (UDP)-glucose, which serves as a bioactive glycosyl donor for various metabolic processes. In this study, a sucrose synthase gene named CtSus was cloned from Cistanche tubulosa, a traditional Chinese medicine known for its rich content of diverse glycosides, based on transcriptome analysis results. The open reading frame of CtSus was 2 418 bp long encoding 805 amino acids. Sequence analysis revealed conserved domains associated with the plant sucrose synthase family at both the N-terminal and C-terminal regions of CtSus protein. Phylogenetic analysis demonstrated that CtSus shares a close evolutionary relationship with sucrose synthases from other plants within the same order. Functional identification of CtSus was performed through whole-cell catalysis coupling with UGT71BD1, a characterized glycosyltransferase enzyme. The results showed that the introduction of CtSus significantly enhanced the conversion rate of glycosylation catalyzed by UGT71BD1. The soluble expression of CtSus in Escherichia coli was further achieved using the pCold^TM TF expression vector. In vitro enzymatic assay indicated the activity of CtSus to catalyze the formation of UDP-glucose in the presence of sucrose and UDP. Real-time quantitative-polymerase chain reaction results showed that the expression patterns of CtSus gene in different parts of C. tubulosa and the suspension cell cultures of C. tubulosa under drought stress correlated with the accumulation patterns observed for phenylethanol glycosides, respectively. Furthermore, key amino acids and their interactions between enzyme and substrate were explored based on protein structure prediction and molecular docking results. Overall, our findings identify a sucrose synthase CtSus responsible for the supply of the active glycosyl donor UDP-glucose during the biosynthesis of glycoside products in C. tubulosa and have also provided a gene element that can be utilized in engineering strain construction for glycoside products production.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors not only have good lipid-lowering effects, but also have pleiotropic effects such as improving cardiovascular outcomes, relieving anti-inflammation, relieving oxidative stress and improving vascular endothelium. In recent years, the continuous development of PCSK9 inhibitors provides new ideas for the treatment of cardiovascular diseases. This article reviewed the pleiotropic mechanisms of PCSK9 inhibitors, especially on vascular endothelial function.

Objective:To investigate the genomic manifestation and pathogenesis of osteosarcoma with different relapse pattens, which were respectively initially presented with bone metastasis or pulmonary metastasis.Methods:From May 1, 2021 to October 1, 2021, 38 fresh tumor specimens and some paraffin-embedded specimens of high-grade osteosarcoma were collected in Peking University People's Hospital, including 29 males and 9 females, aged 19.6±2.2 years (range, 6-61 years). Among the 38 cases, 12 cases had initial bone metastasis (group A) and 26 cases had initial lung metastasis (group B), of which 15 cases (40%, 15/38) had paired specimens of primary and metastatic lesions. Based on Illumina NovaSeq 6000, we analyzed whole-exome sequencing (WES) as well as transcriptome for osteosarcoma with paired samples in different relapse patterns. During all their treatment courses, we also collected their paired samples to reveal these tumors' evolution. We sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms.Results:We found that osteosarcoma in group A mainly carried single-nucleotide variations (83%, 10/12), displaying higher tumor mutation burden [4.9 (2.8, 12.0) & 2.4 (1.4, 4.5), P=0.010] and neoantigen load [743.0 (316.5, 1,034.5) & 128.5 (49.0, 200.5), P=0.003], while those in group B mainly exhibit structural variants (58%, 15/26). The mutation spectrum showed that there was a significant difference in age-related gene imprinting 1 between the bone metastasis group and the lung metastasis group ( P=0.005). Samples were randomly selected from group A (3 patients) to investigate immunologic landscape by multiplex immunohistochemistry, from which we noticed tertiary lymphatic structure from one patient from group A. High conservation of reported genetic sequencing over time was found in their evolving cladograms. Conclusion:Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases with older in age as well as better immunogenicity in tumor microenvironment.

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
Humans ; Signal Transduction ; Stomach Neoplasms/drug therapy* ; Reactive Oxygen Species/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2 ; Cell Line, Tumor

ObjectiveTo study the medication rules of Professor. WANG Xingkuan and inherit his academic experience in the treatment of chest stuffiness and pain with the aid of the Traditional Chinese Medicine Inheritance Computing Platform V3.0 （TCMICS V3.0）. MethodThe original medical records of patients with angina pectoris in coronary heart disease （CHD） diagnosed and treated by Prof. WANG in the outpatient department of Hunan University of Chinese Medicine from 2017 to 2020 were collected and entered into the TCMICS V3.0. The rules of prescriptions and drugs were analyzed by the software. ResultA total of 1 044 prescriptions of Prof. WANG for the treatment of chest stuffiness and pain were collected. Most of the drugs were sweet and bitter in flavor and mainly acted on the lung meridian， followed by heart， spleen， liver， stomach， and kidney meridians. Among the prescriptions， Shengmaisan was the most commonly used classic prescription， and Xintongling No. Ⅲ was the top experienced prescription. High-frequency drugs mainly included Ophiopogonis Radix， Pinelliae Rhizoma， Salviae Miltiorrhizae Radix et Rhizoma， Trichosanthis Pericarpium， Coptidis Rhizoma， Schisandrae Chinensis Fructus， and Bupleuri Radix. The common doses of drugs were 3， 5， 10， and 15 g. The analysis of formulation rules revealed 129 combinations of common drugs， 58 combinations with confidence > 0.99， and the core drugs of common syndromes. Six core drug combinations were obtained by drug clustering. ConclusionProfessor WANG treats chest stuffiness and pain based on syndrome differentiation following the principles of benefiting Qi， nourishing Yin， eliminating phlegm， resolving stasis， soothing liver， and promoting bile secretion， reflecting his academic idea of "regulation of multiple organs and comprehensive treatment". The core prescriptions can be used for reference by clinical practitioners， but further clinical and experimental studies are still needed to verify their efficacy.

Objective:To investigate the surgical outcome and prognostic factors of para-split laminotomy for removal of lumbar spinal canal tumors.Methods:Retrospectively review the clinical data of 35 patients suffering lumbar spinal canal tumors, who underwent the para-split laminotomy for tumor resection in Department of Neurosurgery, Clinical Medical College of Yangzhou University from October 2016 to August 2019, including 16 males and 19 females, and the age was(40.1±10.6)years. Intraoperative blood loss, operation time, tumor resection, tumor pathological results, perioperative complications were observed. Follow-up situations, including tumor recurrence, bony fusion of laminae and spinal stability. Follow-up using outpatient examination and telephone interview was performed by the end of August 2022. The JOA back pain scoring system was used to evaluate the neurological function of the spinal cord, and paired t-test were performed to compare the overall preoperative and postoperative spinal cord neurological function scores. Linear regression and multiple linear regression were used to analyze the prognostic factors. Measurement data of normal distribution were expressed as mean±standard deviation ( ± s), and the comparison before and after operation was performed by paired t-test. Mearsurement data of skewed distribution were expressed as M( Q1, Q3). Count data were expressed as cases. Results:The tumors of 35 patients were resected completely. The median blood loss was 100(75, 140)mL and the average operative duration was (181.1±42.7) min. The postoperative pathological results were as follows: 24 neurilemmomas, 6 meningiomas, 4 ependymomas and 1 neurofibroma. There were no surgery-related complications occurred. The postoperative follow-up ranged from 36 to 69 months, with no tumor recurrence or spinal instability, and bony fusion of laminae seen in some patients on CT imaging. The overall spinal cord neurological function scores of pre and post operation were(19.5±3.4)versus(25.4±2.2), Paired t-test analysis revealed a significant difference between the overall postoperative spinal cord neurological function scores and the preoperative scores, and the postoperative scores were better than the preoperative scores( P<0.05). Multiple linear regression analysis showed a positive correlation between preoperative JOA scores and postoperative JOA scores, and postoperative JOA scores has negative correlation with tumor volume and the age at the time of operation ( P<0.05). Conclusion:Para-split laminotomy with less damage to the posterior spinal structures can effectively improve the neurological function of the spinal cord and protect the stability of the lumbar spine in patients with lumbar spinal canal tumors, and the better the preoperative neurological function of the spinal cord, the better the prognosis of patients, and the smaller the tumor volume, the better the prognosis.