Objective To observe the changes of pleth variability index ( PVI) and central venous pressure ( CVP) in patients undergo-ing resection operation of brain neoplasms,and the correlation of PVI with CVP was investigated. Methods Forty-two patients ( ASA Ⅱ~Ⅲ grade) undergoing elective resection operation of brain neoplasms were included in the study. PVI was monitored continously with Masio Radical-7 pulse oximeter after patient entering operative room. CVP was monitored after central venous catheterization placed with regional an-esthesia. Total intravenous anesthesia was chosen. CVP and PVI were recorded at the time of entering operative room,operation began,and 30 minutes,60 minutes,90 minutes,120 minutes after the beginning of operation. Results The correlation coefficient of PVI with CVP was 0. 201 under spontaneously breathing ( at patient entering operative room before anesthesia) and was 0. 237 under mechanical ventilation. Conclusion Correlation of PVI and CVP is lower. The value of PVI might need further research for guiding volume management.

Objective To evaluate the effects of parecoxib sodium for preemptive analgesia in patients undergoing cerebral angiography. Methods Sixty patients undergoing cerebral angiography were divided into two groups by random digits table with 30 cases in each : group P and group F. Patients in group P received parecoxib sodium 40 mg 30 min before operation, while group F received fentanyl 1 μ g/kg 2 min before operation. The changes of hemodynamics were observed before operation (To), immediately right internal carotid artery angiography during operation (T1), immediately right vertebral artery angiography (T2),immediately left internal carotid artery angiography(T3), immediately left vertebral artery angiography(T4), 10min after operation (T5). The mean arterial pressure (MAP), heart rate (HR), pulse oxygen saturation (SpO2)and visual analogue score (VAS) were recorded at different times during the whole operation. Results There were no significantly differences on MAP, HR and VAS between group P and group F (P ＞ 0.05 ). But the SpO2 at T1 ,T2,T3 in group F (0.94±0.03,0.95±0.02,0.95±0.02) were significantly lower than those in group P (0.98 ± 0.01,0.98 ± 0.02,0.98 ± 0.02 )(P＜0.05 ), and 2 cases SpO2 ＜ 0.90 at Ti. Conclusion Parecoxib sodium administered preemptively provides a nice analgesic effect in patients undergoing cerebral angiography, and is more safe than fentanyl.

PurposeConventional gastric CT provides poor contrast for gastric cancer lesions, the purpose of this study is to investigate the application value of dual energy CT image fusion technology in the improvement of lesion contrast in gastric cancer.Materials and Methods Abdominal dual energy contrast-enhanced CT images of 30 gastric cancer patients were retrospectively analyzed, dual-energy images were reconstructed with different linear and nonlinear fusion settings, contrast between lesions and normal gastric wall, lesion contrast to noise ratio (CNR) were compared among 100 kVp, 140 kVp and different fusion groups, and image quality was evaluated subjectively.Results There were statistically significant differences among the gastric cancer contrast and CNR of 100 kVp, 140 kVp and three linear blending images (F=29.6 and 26.1,P<0.001), with M=0.7 linear fusion group showing the highest CNR. The gastric cancer contrast and CNR was signiifcantly higher with a bandwidth (BW) of 0 HU when compared among the three groups of nonlinear blending images (F=268.5 and 49.5,P<0.001). Moreover, the nonlinear group with a width of 0 HU had a 36% and 47% increase in lesion contrast and CNR over that of a linear blending image. In the subjective evaluation of images, the BW=0 HU nonlinear fusion image was most frequently estimated as the most preferred images for lesion observation of gastric cancer.Conclusion Nonlinear blending with a BW of 0 HU improves display of gastric cancer, and has the potential clinical value to increase the accuracy of staging.

Objective To observe the leading effect of end-tidal pressure of carbon dioxide in artery ( PET CO2 ) on mechanical ventila-tion in New Zealand white rabbits, and to establish parameters for medical animal experiments in terms of hemodynamics, blood gas, blood glucose, electrolyte. Methods 31 anesthetized New Zealand rabbits were practiced tracheostomy tube and mechanical ventilation. Respira-tion rate was 40 breaths/min and tidal volume was adjusted so that PET CO2 was 29 mmHg. Invasive blood pressure, electrocardiogram and PET CO2 were monitored. Blood gas analysis, electrolyte, hemoglobin and blood glucose were tested. Results When PET CO2 was maintained at 29 mmHg, the results were as follows:PH (7.42 ±0.07), 95% confidenceinterval (7.40~7.45);PaCO2(38.5 ±5.8) mmHg, 95%confidenceinterval (36. 4~40. 6) mmHg;BE (1. 45 ± 2. 80) mmol/L,95% confidenceinterval (0. 43~2. 48) mmHg. Conclusion Moni-toring of PET CO2 is good to guide mechanical ventilation in New Zealand white rabbits.

Objective:To investigate the diagnostic performance of continuous-time random-walk (CTRW) diffusion model combined with vesical imaging-reporting and data system (VI-RADS) in the diagnosis of muscle invasion of bladder cancer.Methods:In this case-control study, 64 patients with pathologically confirmed bladder urothelial carcinoma in Peking University First Hospital were retrospectively enrolled from August 2022 to March 2023. The patients were divided into the muscle invasive bladder cancer (MIBC) group and the nonmuscle invasive bladder cancer (NMIBC) group (29 cases and 35 cases, respectively) according to the pathological results. All patients underwent bladder MRI within 4 weeks before surgery, including T 2WI, conventional diffusion weighted imaging (DWI), and multi-b-value DWI. The CTRW model was used to obtain three quantitative diffusion parameters, including D m (an anomalous diffusion coefficient), α (related to temporal diffusion heterogeneity), and β (related to spatial diffusion heterogeneity). The apparent diffusion coefficient (ADC) was calculated using a mono-exponential model. The VI-RADS scores were evaluated based on T 2WI and conventional DWI. The Mann-Whitney U test was used to compare the diffusion parameters between the MIBC group and the NMIBC group. The combination of the parameters was investigated with logistic regression analysis. The diagnostic performance for muscle invasion of bladder cancer was evaluated by receiver operating characteristic analysis and the area under the curve (AUC). The difference between AUC was compared using the DeLong test. Results:There were statistically significant differences in ADC, D m, and α between the MIBC group and the NMIBC group ( Z=-2.31, -2.91, -3.97, P=0.021, 0.004,<0.001). No significant difference was found in β between the two groups ( Z=1.69, P=0.091). The AUC (95% CI) of D m and α for diagnosing MIBC were 0.712 (0.587-0.838) and 0.790 (0.676-0.904) respectively, both of which were higher than that of ADC (AUC 0.669, 95% CI 0.537-0.801) with statistically significant differences ( Z=2.86, 2.27, P=0.004, 0.023). The AUC (95% CI) of CTRW (D m+α) was 0.782 (0.661-0.876), which was significantly higher than that of ADC ( Z=2.35, P=0.019). The AUC (95% CI) of VI-RADS score and VI-RADS combined with CTRW parameter (VI-RADS+D m+α) were 0.823 (0.716-0.930) and 0.900 (0.799-0.961) respectively, with a statistically significant difference between them ( Z=2.16, P=0.031). Conclusion:The D m and α parameters in the CTRW diffusion model show better performance than the ADC in the mono-exponential model for muscle-invasive evaluation of bladder cancer, and the CTRW diffusion model can enhance the diagnostic performance of VI-RADS.

BACKGROUND: Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer. METHODS: Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. RESULTS: lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. CONCLUSION Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.
Humans ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic/genetics* ; MAP Kinase Signaling System ; MicroRNAs/metabolism* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; RNA, Long Noncoding/metabolism* ; Triple Negative Breast Neoplasms/pathology*

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.

OBJECTIVE： To explore the component， target and pathway of Panax notoginseng for coronary heart disease （CHD） and its potential molecular mechanism. METHODS： Based on network pharmacology， active components of P. notoginseng were retrieved with TCMSP platform. The targets of P. notoginseng for CHD were screened by using DRAR-CPI server， GeneCards and DisGeNET databases. Cytoscape 3.6.0 software was used to form the effective components-CHD targets network of P. notoginseng. String database was used to draw target interaction network. Network Analyzer tool was used to calculate target connectivity， and potential core targets were screened. Molecular docking between the core targets and the effective components of P. notoginseng was performed by Systems Dock Web Site server. KEGG pathway enrichment analysis and gene ontology （GO） enrichment analysis were also carried out to explore the important signal pathway and molecular function of P. notoginseng for CHD. “Effective component-target-signal pathway”network of important signal pathway were constructed. RESULTS： Five effective components （stigmasterol， β-sitosterol， ginsenoside rh2， quercetin， notoginsenoside r1） were screened from P. notoginseng for CHD， which acted on 96 targets and had 134 functional relationships. Five core targets were protein kinase B （AKT）， interleukin 6 （IL-6）， vascular endothelial growth factor A （VEGFA）， c-JUN protein （c-JUN） and heparin binding epidermal growth factor （HB-EGF）， which played an important role in the treatment of CHD by altering protein binding and regulating signaling pathways as phosphatidylinositol-3 kinase-protein/kinase B （PI3K/AKT）， hypoxia-inducible factor-1 （HIF-1） and mitogen-activated protein kinase （MAPK）. CONCLUSIONS： P. notoginseng in the treatment of CHD is not only play a variety of effects through the role of multiple targets， but also produce complex network regulation effect through the interaction between targets.

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.