Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Hepatitis E is an acute and self-limiting viral hepatitis caused by the hepatitis E virus (HEV). It has a higher mortality rate among immunosuppressed patients and pregnant women infected with HEV. Although HEV infections in humans are mostly caused by contaminated water or food worldwide, the incidence of transfusion-transmitted hepatitis E is continuously rising. Additionally, the prevalence of serum anti-HEV IgG in the blood donors in China is at a relatively high level, making it worth considering screening blood donors for HEV. This article briefly reviews the globally reported cases of transfusion-transmitted hepatitis E and the HEV screening strategies for blood donations.

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

OBJECTIVE To report a case of hepatitis B virus （HBV） reactivation induced by iparomlimab and tuvonralimab， summarize the clinical characteristics and potential mechanisms of such adverse reactions induced by immune-checkpoint inhibitors （ICIs）， and provide references for clinical application. METHODS From the perspective of a clinical pharmacist， a retrospective analysis was conducted on the treatment course of a patient with metastatic cervical cancer who experienced HBV reactivation after receiving iparomlimab and tuvonralimab. Additionally， an analysis of the correlation with adverse reactions was performed， and the clinical characteristics， risk factors， potential mechanisms， key points of treatment approaches and pharmaceutical care associated with HBV reactivation induced by ICIs were summarized. RESULTS & CONCLUSIONS The patient developed HBV reactivation and severe liver injury after using iparomlimab and tuvonralimab. The condition improved following drug discontinuation， and symptomatic treatment such as glucocorticoids. According to Naranjo’s Assessment Scale and China’s Measures for the Reporting and Monitoring of Adverse Drug Reactions， the association between iparomlimab and tuvonralimab and HBV reactivation was judged as “highly probable”， and it was identified as a new adverse reaction； the correlation between iparomlimab and tuvonralimab， paclitaxel and liver injury was “highly probable”. HBV reactivation in hepatitis B patients receiving standardized antiviral therapy is very rare after ICIs treatment； HBV reactivation is related to the overactivation of the immune system and disruption of immune balance induced by ICIs. For such patients， glucocorticoids should be administered for treatment， accompanied by pharmaceutical care， including pre- medication risk assessment and monitoring of relevant indicators during treatment.

BACKGROUND:Mechanical factors can affect the angiogenic ability of vascular endothelial cells.How the vessel number affects the hydrodynamic properties of microvessels remains to be clarified. OBJECTIVE:To investigate the influence of vessel number on the hydrodynamics of vascular networks based on computational fluid dynamics. METHODS:Three three-dimensional models of vascular network with different vessel numbers were constructed using the Geometry module of ANSYS 19.0 software,and then the vascular network was meshed to tetrahedral elements in Mesh module.The vascular network was assumed to rigid wall without slip,and the blood was assumed to laminar,viscous,and incompressible Newtonian fluid.Blood density,velocity,and a series of blood viscosity coefficients were also established.The Navier-Stokes equation was used for calculation.Hydrodynamic properties of different parts of vascular network with different vessel numbers were analyzed and compared. RESULTS AND CONCLUSION:The streamline,velocity,and mass flow all had the same trend in the vascular network,that is,the outlet and inlet were higher and the middle junction of vascular network was lower.The more the number of vessels,the thinner the blood flow lines in each part of the vascular network.Also,the velocity,mass flow,and wall shear decreased with the increase of the number of blood vessels.Therefore,the changes in vessel number could influence the hydrodynamic environment in the vascular network.Computational fluid dynamics indicates that the changes in vessel numbers can influence the hydrodynamic properties of blood,and provides a new idea for treating bone hypoperfusion-induced diseases(fracture nonunion,bone defect,osteoporosis,etc.)through tonifying kidney and activating blood circulation based on the coupling between angiogenesis and osteogenesis.

Objective:To investigate the effects of astragaloside IV (AS-IV) on acute myocardial injury in rats with high-level spinal cord injury (SCI).Methods:Twenty-four healthy male SD rats, aged 8-10 weeks with a body weight of 250-300 g, were randomly divided into 4 groups using a random number table method: sham operation group, high-level SCI group (SCI group), high-level SCI+AS-IV group (SCI+AS-IV group) and high-level SCI+AS-IV+silent information regulator 1 (SIRT1) inhibitor EX527 group (SCI+AS-IV+EX527 group), with 6 rats in each group. The SCI model was established using the modified Allen method and the sham operation group underwent the spinal cord exposure only. In the SCI+AS-IV group, 40 mg/kg of AS-IV was injected intraperitoneally immediately after injury. SCI+AS-IV+EX527 group received an intraperitoneal injection of 5 mg/kg EX527 at one hour before injury and another injection of 40 mg/kg AS-IV in the same way immediately after injury. The sham operation group and the SCI group received an equal volume of saline via intraperitoneal injection. Immediately after awakening from injury, the hind limb motor function of the rats in each group was observed, recorded and then evaluated using the BBB method. At 24 hours after injury, the ultrastructure of the cardiomyocytes was examined under a transmission electron microscope; the levels of serum cardiac troponin I (cTnI), myocardial tissue inflammatory factors interleukin (IL)-18 and IL-1β were quantified by the ELISA method; the level of reactive oxygen species (ROS) of the myocardial tissue was assessed utilizing the dihydroethidium (DHE) assay; biochemical analyses were employed to determine the superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentrations; mRNA and protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (caspase-1), gasdermin D (GSDMD), SIRT1 and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) were examined using RT-PCR and Western blot; cardiomyocyte pyroptosis rate was evaluated by caspase-1 and TUNEL double-labeled fluorescence staining.Results:Immediately after awakening from injury, the sham operation group exhibited normal hind limb activity, with BBB scores of 21(21, 21)points, while the remaining groups displayed flaccid paralysis in both hind limbs, accompanied by the cessation of spontaneous excretion, with BBB scores of 0(0, 0)points. At 24 hours after injury, transmission electron microscopy did not reveal any significant abnormalities in the ultrastructure of the myocardiomyocytes in the sham operation group, while changes of varying degrees were observed in the SCI group. The ELISA results indicated that at 24 hours after injury, the serum cTnI level in the SCI group was (1 435.3±148.1)pg/ml, higher than (619.6±95.4)pg/ml in the sham operation group ( P<0.01); the cTnI level was (1 154.0±80.0)pg/ml in the SCI+AS-IV group, lower than that in the SCI group ( P<0.01); the cTnI level was (1 321.8±50.2)pg/ml in the SCI+AS-IV+EX527 group, higher than that in the SCI+AS-IV group ( P<0.05). The levels of IL-18 and IL-1β in the myocardial tissue in the SCI group were (493.0±145.0)pg/ml and (936.7±93.2)pg/ml, higher than (131.1±62.5)pg/ml and (281.7±83.6)pg/ml in the sham operation group ( P<0.01); the levels of IL-18 and IL-1β in the SCI+AS-IV group were (182.4±45.6)pg/ml and (573.4±99.5)pg/ml, lower than those in the SCI group ( P<0.01); the levels of IL-18 and IL-1β in the SCI+AS-IV+EX527 group were (337.4±72.0)pg/ml and (742.6±82.7)pg/ml, higher than those in the SCI+AS-IV group ( P<0.05), yet lower than those in the SCI group ( P<0.01). At 24 hours after injury, DHE and biochemical assays showed that the levels of ROS and MDA in the myocardial tissue in the SCI group were (65±6)% and (1.97±0.27)nmol/mg, higher than (19±10)% and (1.03±0.16)nmol/mg in the sham operation group ( P<0.01); the ROS and MDA levels in the SCI+AS-IV group were (37±10)% and (1.39±0.11)nmol/mg, lower than those in the SCI group ( P<0.01); the ROS and MDA levels in the SCI+AS-IV+EX527 group were (52±7)% and (1.70±0.14)nmol/mg, higher than those in the SCI+AS-IV group ( P<0.05). The SOD level in the myocardial tissue of the SCI group was (658.48±77.56)U/mg, lower than (1 059.55±71.91)U/mg in the sham operation group ( P<0.01); the SOD level in the SCI+AS-IV group was (901.74±32.30)U/mg, higher than that in the SCI group ( P<0.01); the SOD level in the myocardial tissue in the SCI+AS-IV+EX527 group was (799.86±26.70)U/mg, lower than that in the SCI+AS-IV group ( P<0.05). At 24 hours after injury, RT-PCR showed that the mRNA expression levels of NLRP3, caspase-1 and GSDMD in the myocardial tissue of the SCI group were 2.07±0.25, 2.46±0.28 and 1.82±0.12 respectively, which were higher than 1.10±0.13, 0.95±0.17 and 1.03±0.08 in the sham operation group ( P<0.01); the mRNA expression levels of NLRP3, caspase-1 and GSDMD in the SCI+AS-IV group were 1.47±0.24, 1.51±0.16 and 1.42±0.13 respectively, which were lower than those in the SCI group ( P<0.01); the mRNA expression levels of NLRP3, caspase-1 and GSDMD in the SCI+AS-IV+EX527 group were 1.93±0.28, 1.97±0.31 and 1.65±0.16 respectively, which were higher than those in the SCI+AS-IV group, yet lower than those in the SCI group ( P<0.05). The mRNA expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI group were 0.41±0.09 and 0.56±0.07, lower than 1.20±0.14 and 1.29±0.20 in the sham operation group ( P<0.01); the mRNA expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI+AS-IV group were 0.78±0.08 and 1.01±0.19, higher than those of the SCI group ( P<0.01); the mRNA expression levels of SIRT1 and PGC-1α in the myocardial tissue of the SCI+AS-IV+EX527 group were 0.53±0.12 and 0.72±0.22, lower than those of the SCI+AS-IV group ( P<0.05). At 24 hours after injury, the western blot analysis showed that the protein expression levels of NLRP3, caspase-1 and GSDMD in the myocardial tissue in the SCI group were 1.00±0.20, 0.60±0.19 and 0.77±0.15 respectively, which were higher than 0.27±0.09, 0.18±0.10 and 0.28±0.08 in the sham operation group ( P<0.01); the protein expression levels of NLRP3, caspase-1 and GSDMD in the SCI+AS-IV group were 0.59±0.10, 0.25±0.11 and 0.33±0.11 respectively, lower than those in the SCI group ( P<0.01); the protein expression levels of NLRP3, caspase-1 and GSDMD in the myocardial tissue in the SCI+AS-IV+EX527 group were 0.85±0.15, 0.54±0.12 and 0.55±0.13 respectively, higher than those in the SCI+AS-IV group ( P<0.05). The protein expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI group were 0.44±0.16 and 0.28±0.10, lower than 0.93±0.22 and 0.75±0.16 in the sham operation group ( P<0.01); the protein expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI+AS-IV group were 0.78±0.19 and 0.55±0.12, higher than those in the SCI group ( P<0.01); the protein expression levels of SIRT1 and PGC-1α in the myocardial tissue in the SCI+AS-IV+EX527 group were 0.46±0.16 and 0.35±0.07, lower than those in the SCI+AS-IV group ( P<0.05). At 24 hours after injury, caspase-1 and TUNEL double-labeled fluorescence staining showed that the cardiomyocyte pyroptosis rate in the SCI group was (34.5±6.7)%, higher than (5.3±2.9)% in the sham operation group ( P<0.01); the cardiomyocyte pyroptosis rate in the SCI+AS-IV group was (13.4±3.0)%, lower than that in the SCI group ( P<0.01); the cardiomyocyte pyroptosis rate in the SCI+AS-IV+EX527 group was (22.5±5.9)%, higher than that in the SCI+AS-IV group ( P<0.01), yet lower than that in the SCI group ( P<0.01). Conclusions:AS-IV can significantly reduce acute myocardial injury in rats with high-level SCI. Its mechanism may involve activating the myocardial SIRT1/PGC-1α signaling pathway, protecting the mitochondria, enhancing the ability to resist oxidative stress, and effectively inhibiting the NLRP3 inflammasome-mediated pyroptosis pathway.

OBJECTIVE To study the unknown impurity in potassium aspartate and magnesium aspartate injection by heart-cutting two-dimensional liquid chromatography coupled with Quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF-MS). METHODS The Waters ACQUITY UPLC 2D system and Xevo G2-XS QTof-MS system were used. One- dimensional chromatographic conditions were as listed. An Agilent ZORBAX-NH2 column was used, and potassium dihydrogen thophosphate(0.05 mol·L-1)-acetonitrile(37∶63) as the mobile phase, at a flow rate of 1.3 mL·min-1. The detection wavelength was set at 200 nm. Two-dimensional chromatographic conditions were as listed. A Waters ACQUITY UPLC HSS T3 column was used, and 0.1% formic acid solution(ESI+)/5 mmol·L-1 ammonium formate(ESI-) as the mobile phase A, and acetonitrile as the mobile phase B, in gradient mode. The mass spectrometry used an electro spray ionization source(ESI) for positive and negative ion mode detection. RESULTS Combined the high resolution mass, MS2 fragment ions and the UNIFI software, the possible structure of the unknown impurity in potassium aspartate and magnesium aspartate injection was infered. CONCLUSION The 2D-LC-Q-TOF-MS method can be used to identify impurities in potassium aspartate and magnesium aspartate injection, which provides reference for the improvement of quality control and process optimization of potassium aspartate and magnesium aspartate injection.

Objective: To investigate the effect of berberine (BBR) on the proliferation and autophagy of mesangial cells in high glucose (HG) environment and the specific molecular mechanism． Methods: Mesangium cells at exponential growth stage were divided into the following groups : normal group，high glucose group，high glucose + BBR treatment group (30，60 and 90 μmol / L) ，high glucose + BBR (90 μmol / L) + AMPK inhibitor Compound C group ( CC group) ; the number of mesangial cells was calculated by high content cell imager．The expressions of type Ⅳ collagen ( Col-Ⅳ) ，fibronectin (FN) and microtubule-associated protein 1 light chain 3B (LC3B) in mesangial cells were detected by immunofluorescence assay．The protein expression levels of LC3B，Beclin-1， p62，Col-Ⅳ , FN and silencing regulatory factor 1 (SIRT1) / adenylate activated protein kinase (AMPK) signaling pathway were detected by Western blot. Results: Compared with the normal group ，high content cell imaging showed abnormal proliferation of mesangial cells in the hyperglycemic group．The results of immunofluorescence and Western blot showed that the expression levels of Col-Ⅳ and FN deposited in mesangial extracellular matrix increased in the high glucose group．The results of Western blot showed that the protein expressions of SIRT1，p- AMPK，LC3B and Beclin-1 decreased，while the protein expressions of p-p65 and p62 increased．BBR inhibited the abnormal proliferation of mesangial cells induced by high glucose．BBR could reduce the expression levels of Col-Ⅳ and FN deposited in mesangial extracellular matrix． BBR could increase the expressions of SIRT1 ，p- AMPK，LC3B and Beclin-1 proteins in mesangial cells，while decrease the expressions of p-p65 and p62 proteins. CC group weakened the inhibition of mesangial cell proliferation and autophagy by high dose BBR. Conclusion Berberine can effectively inhibit the proliferation of mesangial cells induced by high glucose and increase the level of autophagy，which may be related to SIRT1 / AMPK signaling pathway.

OBJECTIVE To establish a method for the determination of fourteen fluorescent whitening agents in cosmetics by HPLC-MS/MS. METHODS Samples were extracted on a Waters ACQUITY UPLC ®BEH C18(2.1 mm×50 mm, 1.7 μm) column after ultrasonic extracted by DMF with the mobile phase consisted of methanol-0.1% ammonia water solution by gradient elution. The flow rate was 0.3 mL·min-1. The column temperature was 40 ℃. MS was performed using triple quadrupole mass spectrometry. Electrospray ionization source was operated in the positive/negative mode using multiple reaction monitoring scanning mode. RESULTS The results showed that there were good linear relationships for the fluorescent whitening agents in a certain concentration range with correlation coefficients(r) greater than 0.99. The limits of quantification were 0.01-20 μg·g-1 and the limits of detection were 0.004-8 μg·g-1. The average recoveries at three spiked levels were in the range of 85.4%-108.9%, and the relative standard deviation were in the range of 0.3%-7.2%. CONCLUSION The method has high sensitivity, strong specificity, simple and convenient operation, and is suitable for the detection of fourteen fluorescent whitening agents in cosmetics.

Objective:To seek any correlation between cortical activity and the swallowing of dysphagia patients with infratentorial stroke, and to observe any effect of three-needle acupuncture of the tongue on such activity.Methods:Thirty infratentorial stroke survivors with dysphagia were randomly divided into a tongue three-needle group and a sham acupuncture group, each of 15. Functional near-infrared spectroscopy was used to monitor changes in the concentration of oxygenated hemoglobin (ΔHbO 2) at rest, during acupuncture (or sham acupuncture), during real or sham electro-acupuncture, and at rest after the acupuncture or sham acupuncture treatment. The Modified Rankin Scale, a Penetration-Aspiration Scale (PAS), and the Functional Oral Intake Scale were employed to assess overall functional disability and the swallowing of both groups. Results:At rest the average ΔHbO 2 concentrations recorded in the left primary motor cortex, the left dorsolateral prefrontal cortex and the left premotor cortex in both groups were positively correlated with the PAS scores. During the acupuncture ΔHbO 2 concentration in the right inferior frontal gyrus and the left middle temporal gyrus increased significantly in the tongue three-needle group. It decreased significantly in the left somatosensory cortex and the left primary motor cortex. Conclusion:Three-needle acupuncture of the tongue induces changes in cortical activity in infratentorial stroke survivors with dysphagia, suggesting a potential technique for improving disordered swallowing.