Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

Objective To evaluate and compare the long-term efficacy of endoscopic radiofrequency ablation(RFA)and photodynamic therapy(PDT)combined with biliary stenting for the treatment of unresectable extrahepatic cholangiocarcinoma.Methods Clinical data of patients with cholangiocarcinoma who received endoscopic RFA or PDT treatment from February 2018 to February 2023 were retrospectively collected.The patients were divided into RFA group(n=30,received endoscopic RFA combined with biliary stent placement)and PDT group(n=20,received PDT combined with biliary stent placement).The frequency of treatment,stent patency time,overall survival time and adverse events incidence were counted.The factors affecting the survival time of patients were analyzed.Results The overall survival time was 14.0(95%CI:11.8～16.2)months in RFA group and 18.0(95%CI:15.4～20.6)months in PDT group,the median patency time of stent was 4.0(95%CI:2.7～5.3)months in RFA group and 3.5(95%CI:2.3～4.7)months in PDT group,the differences were not statistically significant(P>0.05).Multivariate Cox regression analysis showed that the H＾R of patients with≥2 endoscopic RFA or PDT treatments was 2.417,which was a protective factor affecting overall survival(P=0.018),while the H＾R of TNM stage Ⅲ to Ⅳ was 0.300,which was a risk factor affecting the overall survival period(P=0.002).No significant difference was found in clinical success rate(both 100.00%)and adverse events incidence between the two groups[28.13%(9/32)vs.23.81%(5/21)],the difference was not statistically significant(P>0.05).Conclusion The long-term efficacy of endoscopic RFA or PDT combined with biliary stenting in the treatment of unresectable extrahepatic cholangiocarcinoma is comparable,while the sequential treatment of endoscopic RFA or PDT≥2 times can effectively prolong the overall survival of patients.

Objective To evaluate and compare the long-term efficacy of endoscopic radiofrequency ablation(RFA)and photodynamic therapy(PDT)combined with biliary stenting for the treatment of unresectable extrahepatic cholangiocarcinoma.Methods Clinical data of patients with cholangiocarcinoma who received endoscopic RFA or PDT treatment from February 2018 to February 2023 were retrospectively collected.The patients were divided into RFA group(n=30,received endoscopic RFA combined with biliary stent placement)and PDT group(n=20,received PDT combined with biliary stent placement).The frequency of treatment,stent patency time,overall survival time and adverse events incidence were counted.The factors affecting the survival time of patients were analyzed.Results The overall survival time was 14.0(95%CI:11.8～16.2)months in RFA group and 18.0(95%CI:15.4～20.6)months in PDT group,the median patency time of stent was 4.0(95%CI:2.7～5.3)months in RFA group and 3.5(95%CI:2.3～4.7)months in PDT group,the differences were not statistically significant(P>0.05).Multivariate Cox regression analysis showed that the H＾R of patients with≥2 endoscopic RFA or PDT treatments was 2.417,which was a protective factor affecting overall survival(P=0.018),while the H＾R of TNM stage Ⅲ to Ⅳ was 0.300,which was a risk factor affecting the overall survival period(P=0.002).No significant difference was found in clinical success rate(both 100.00%)and adverse events incidence between the two groups[28.13%(9/32)vs.23.81%(5/21)],the difference was not statistically significant(P>0.05).Conclusion The long-term efficacy of endoscopic RFA or PDT combined with biliary stenting in the treatment of unresectable extrahepatic cholangiocarcinoma is comparable,while the sequential treatment of endoscopic RFA or PDT≥2 times can effectively prolong the overall survival of patients.

Objective:To observe the effects of tetrandrine tablets combined with montelukast sodium on respiratory function,inflammatory mediators,serum matrix metalloproteinase-9(MMP-9)and basic fibroblast growth factor(bFGF)levels in pneumoconiosis patients.Methods:120 pneumoconiosis patients who were admitted to our hospital from January 2023 to June 2024 were selected,they were divided into control group(montelukast sodium treatment,n=60)and study group(tetrandrine tablets combined with montelukast sodium treatment,n=60)by random number table method.The pulmonary function indexes[first second forced expiratory volume(FEV1),forced vital capacity(FVC),maximum ventilation volume(MVV)],6-minute walking test(6MWT)disitance,St.George Respiratory Questionnaire(SGRQ)score,Improved Medical Research Council Dyspnea(mMRC)index,and inflammatory mediators[Cystatin C(Cys C),interleukin-2 receptor(IL-2R),C-reactive protein(CRP)]and serum MMP-9,bFGF levels were compared between the two groups.The occurrence of adverse reactions were observed.Results:FEV1,FVC,MVV,6MWT distance in the study group at 6 months after treatment were higher than those in the control group,and SGRQ score,mMRC index,CysC,IL-2R,CRP,MMP-9,bFGF were lower than those in the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Tetrandrine tablets combined with montelukast sodium in the treatment of pneumoconiosis patients can effectively improve respiratory function,increase exercise endurance,regulate inflammatory mediators and serum MMP-9,bFGF levels,which is safe and reliable.

Objective:To observe the effects of tetrandrine tablets combined with montelukast sodium on respiratory function,inflammatory mediators,serum matrix metalloproteinase-9(MMP-9)and basic fibroblast growth factor(bFGF)levels in pneumoconiosis patients.Methods:120 pneumoconiosis patients who were admitted to our hospital from January 2023 to June 2024 were selected,they were divided into control group(montelukast sodium treatment,n=60)and study group(tetrandrine tablets combined with montelukast sodium treatment,n=60)by random number table method.The pulmonary function indexes[first second forced expiratory volume(FEV1),forced vital capacity(FVC),maximum ventilation volume(MVV)],6-minute walking test(6MWT)disitance,St.George Respiratory Questionnaire(SGRQ)score,Improved Medical Research Council Dyspnea(mMRC)index,and inflammatory mediators[Cystatin C(Cys C),interleukin-2 receptor(IL-2R),C-reactive protein(CRP)]and serum MMP-9,bFGF levels were compared between the two groups.The occurrence of adverse reactions were observed.Results:FEV1,FVC,MVV,6MWT distance in the study group at 6 months after treatment were higher than those in the control group,and SGRQ score,mMRC index,CysC,IL-2R,CRP,MMP-9,bFGF were lower than those in the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Tetrandrine tablets combined with montelukast sodium in the treatment of pneumoconiosis patients can effectively improve respiratory function,increase exercise endurance,regulate inflammatory mediators and serum MMP-9,bFGF levels,which is safe and reliable.

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to rapidly identify the chemical components in Dracocephalum moldavica, and UPLC was employed to determine the content of its main components. MS analysis was performed using an electrospray ionization(ESI) source and data were collected in the negative ion mode. By comparing the retention time and mass spectra of reference compounds, and using a self-built compound database and the PubChem database, 68 compounds were identified from D. moldavica, including 36 flavonoids, 22 phenylpropanoids, 4 phenols, and 6 other compounds. On this basis, a UPLC quantitative method was established to simultaneously determine 8 main components, i.e., luteolin-7-O-glucuronide, apigenin-7-O-glucuronide, rosmarinic acid, diosmetin-7-O-glucuronide, tilianin, acacetin-7-O-glucuronide, acacetin-7-O-(6″-O-malonyl)-glucoside, and acacetin. A Waters ACQUITY BEH C_(18) column(2.1 mm × 100 mm, 1.7 μm) was used, with acetonitrile and a water solution containing 0.1% formic acid and 0.1% phosphoric acid as the mobile phase for gradient elution. The detection wavelength was set at 330 nm, with a flow rate of 0.4 mL·min~(-1), and the column temperature was maintained at 35 ℃. The 8 components demonstrated good linearity(r≥0.999 9) over a wide mass concentration range(50 or 100 times). The average recovery rate ranged from 97.5% to 105.1%, and the relative standard deviations(RSDs) were 0.90% to 3.4%(n= 6), indicating that the method was simple, accurate, and reliable. In 17 batches of D. moldavica samples, the content of these 8 components ranged from 0.405 to 2.10, 0.063 to 0.342, 0.446 to 2.43, 0.415 to 1.47, 1.57 to 4.34, 0.173 to 0.386, 1.00 to 5.40, and 0.069 to 0.207 mg·g~(-1), respectively. These results indicate significant differences in the internal quality of the samples, highlighting the need for strict quality control to ensure their pharmacodynamic efficacy. This study provides a scientific basis for the rapid discovery of pharmacodynamic substances, comprehensive quality control, and the formulation or revision of quality standards for D. moldavica.
Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Lamiaceae/chemistry* ; Flavonoids/chemistry*

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Aim To analyze the differences in plasma biomarkers and metabolic pathways between Atractylodes chinensis and Atractylodes coreana after intervention in spleen deficiency rats, and discuss the spleen strengthening mechanism of the two from a non targeted metabolomics perspective. Methods A spleen deficiency model was established in SD rats using a composite factor method of improper diet, excessive fatigue, and bitter cold diarrhea. To determine the content of gastrointestinal and immunological indicators, UHPLC-QE-MS technology was used, combined with principal component analysis (PC A) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) methods to search for biomarkers in plasma of spleen deficiency rats, and metabolic pathways were induced using the Pathway database. Results After administration of Atractylodes chinensis and Atractylodes coreana, various indicators in plasma of spleen deficiency rats showed varying degrees of regression. Metabolomics analysis showed that Atractylodes chinensis and Atractylodes coreana respectively recalled 70 and 82 plasma differential metabolites. Atractylodes chinensis mainly regulated two metabolic pathways : "Glycine, serine, and threonine metabolism, and "Thiamine metabolism". Atractylodes coreana mainly regulated five metabolic pathways, "Glycine, serine, and threonine metabolism", "Thiamine metabolism, "Pyrimidine metabolism", "Butanoate metabolism", and "Riboflavin metabolism". Conclusions Both Atractylodes chinensis and Atractylodes coreana have certain regulatory effects on spleen deficiency rats, and their mechanism of action may be related to regulating metabolic pathways such as "Glycine, serine, and threonine metabolism, and "Thiamine metabolism"in spleen deficiency.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.