Early neurological deterioration(END)occurs in patients with acute cerebral infarction after recombinant tissue-plasminogen activator(rt-PA)intravenous thrombolysis,which seriously affects the prognosis of patients and even causes death.However,there is no effective treatment.This report describes two patients with acute ischemic stroke presenting with right-sided limb weakness within 4.5 hours of onset.Brain CT ruled out cerebral hemorrhage and both patients were diagnosed with acute ischemic stroke.END occurred within 24 hours after intravenous thrombolysis with rt-PA.Reexamine Brain CT showed no evidence of cerebral hemorrhage.The patients were treated with continuous tirofiban infusion for 48 hours,overlapping with oral antiplatelet therapy for 4 hours and 6 hours,respectively.After discontinuation of tirofiban,no further neurological deterioration was observed.At the 3-month follow-up,there was no recurrence,and the modified Rankin scale(mRS)scores were 1 and 3,respectively.This study delineates the diagnostic and therapeutic trajectories of two paradigmatic cases to inform clinical decision-making for analogous presentations,thereby contributing to evidence-based management strategies.

Objective:To investigate the effect and underlying mechanism of sonodynamic therapy (SDT) on inflammation-related atrial fibrillation (AF) susceptibility.Methods:Lipopolysaccharide (LPS)-stimulated mouse and HL-1 mouse atrial myocyte models were used. (1) In vivo study: experimental groups included control, LPS, LPS+SDT, and SDT groups, with 20 mice in each group. Atrial fibrillation inducibility and duration were assessed by electrical stimulation. Western blot was used to analyze atrial expression of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), interleukin (IL)-1β, and IL-18. Immunohistochemistry was used to detect calcium voltage-gated channel subunit alpha1 C (CACNA1C) expression. (2) In vitro study: cell counting kit-8 (CCK-8) and Western blot were used to determine the optimal and safe LPS concentration. The safe incubation condition for the sonosensitizer sinoporphyrin sodium was determined by CCK-8 and fluorometry. An LPS-induced inflammatory model in HL-1 atrial myocytes was used, with experimental groups including control, LPS, LPS+SDT, LPS+sinoporphyrin sodium, and LPS+ultrasound groups. NLRP3 was overexpressed using plasmid transfection, with experimental groups including control, NLRP3 plasmid, negative control plasmid, and NLRP3 plasmid+SDT groups. SDT was applied to LPS-stimulated or NLRP3-overexpressing HL-1 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to measure mRNA and protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Cleaved Caspase-1, IL-1β, IL-18, and CACNA1C. The NLRP3 inhibitor MCC950 was used to validate the relationship of NLRP3 and CACNA1C. The experimental groups included control, LPS, LPS+MCC950, and MCC950 groups. Intracellular reactive oxygen species (ROS) levels were detected using the probe DCFH-DA, and the ROS scavenger N-acetyl-L-cysteine (NAC) was used to test if the effects of SDT was ROS-dependent.Results:(1) In vivo: The LPS+SDT group exhibited a lower incidence of atrial fibrillation induction and a shorter duration of atrial fibrillation compared to the LPS group(both P<0.05). Protein expression levels of NLRP3 and IL-1β were lower than those in the LPS group (all P<0.05), while the expression of CACNA1C subunit tended to increase relative to the LPS group ( P>0.05). (2) In vitro: The safe concentration of LPS for administration was ≤20 μg/ml, with an optimal pro-inflammatory concentration of 4 μg/ml. The safe concentration of sinoporphyrin sodium for administration was 0.4 μmol/L, with an optimal incubation time of 4 hours. Compared to the LPS group or NLRP3 plasmid group, the LPS+SDT group or NLRP3 plasmid+SDT group exhibited lower expression levels of NLRP3, ASC, Cleaved Caspase-1, IL-1β, and IL-18, and higher mRNA and protein levels of CACNA1C (all P<0.05). The LPS+MCC950 group had higher CACNA1C protein expression than the LPS group ( P<0.05). SDT increased intracellular ROS levels, and NAC blocked the regulatory effects of SDT on NLRP3 and CACNA1C. Conclusion:SDT reduces atrial fibrillation susceptibility in mice by inhibiting NLRP3 inflammasome activation in atrial cardiomyocytes, thereby upregulating the L-type calcium channel subunit CACNA1C.

Diabetic cardiomyopathy （DCM）， a cardiovascular complication caused by diabetes mellitus， is a major cause of heart failure and even sudden cardiac death in diabetic patients. Traditional Chinese medicine （TCM） posits that the core pathogenesis of DCM lies in internal deficiency and superficial excess， characterized by deficiency of both Qi and Yin combined with phlegm and blood stasis. Modern medical treatments for DCM primarily focus on blood glucose control and symptom alleviation yet lack targeted therapeutic strategies. In contrast， TCM offers a wealth of practical experience and a complete theoretical system， demonstrating definite clinical efficacy and high medication safety in DCM management. As a classic formula for tonifying Qi and nourishing Yin， Shengmaisan comprises Ginseng Radix et Rhizoma， Ophiopogonis Radix， and Schisandrae Chinensis Fructus. It contains multiple bioactive components， including ginsenosides， ophiopogonin， schisandrins， and homoisoflavonoids， which exhibit cardioprotective properties. The therapeutic mechanisms of Shengmaisan-like formulae for DCM involve enhancing myocardial contractility， attenuating myocardial fibrosis， modulating mitochondrial quality control， regulating glucose metabolism， mitigating oxidative stress， and suppressing inflammatory responses. Clinically， Shengmaisan-like formulae not only manage hyperglycemic status but also ameliorate cardiac structural and functional impairments and enhance exercise tolerance in DCM patients， playing a vital role in the prevention， treatment， and rehabilitation of DCM. This paper analyzes the feasibility of Shengmaisan-like formulae in DCM management and synthesizes current research achievements regarding their chemical components， mechanisms of action， and clinical applications， aiming to provide a scientific foundation for the use of such formulae in the treatment of DCM.

Early neurological deterioration(END)occurs in patients with acute cerebral infarction after recombinant tissue-plasminogen activator(rt-PA)intravenous thrombolysis,which seriously affects the prognosis of patients and even causes death.However,there is no effective treatment.This report describes two patients with acute ischemic stroke presenting with right-sided limb weakness within 4.5 hours of onset.Brain CT ruled out cerebral hemorrhage and both patients were diagnosed with acute ischemic stroke.END occurred within 24 hours after intravenous thrombolysis with rt-PA.Reexamine Brain CT showed no evidence of cerebral hemorrhage.The patients were treated with continuous tirofiban infusion for 48 hours,overlapping with oral antiplatelet therapy for 4 hours and 6 hours,respectively.After discontinuation of tirofiban,no further neurological deterioration was observed.At the 3-month follow-up,there was no recurrence,and the modified Rankin scale(mRS)scores were 1 and 3,respectively.This study delineates the diagnostic and therapeutic trajectories of two paradigmatic cases to inform clinical decision-making for analogous presentations,thereby contributing to evidence-based management strategies.

Objective:To investigate the effect and underlying mechanism of sonodynamic therapy (SDT) on inflammation-related atrial fibrillation (AF) susceptibility.Methods:Lipopolysaccharide (LPS)-stimulated mouse and HL-1 mouse atrial myocyte models were used. (1) In vivo study: experimental groups included control, LPS, LPS+SDT, and SDT groups, with 20 mice in each group. Atrial fibrillation inducibility and duration were assessed by electrical stimulation. Western blot was used to analyze atrial expression of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), interleukin (IL)-1β, and IL-18. Immunohistochemistry was used to detect calcium voltage-gated channel subunit alpha1 C (CACNA1C) expression. (2) In vitro study: cell counting kit-8 (CCK-8) and Western blot were used to determine the optimal and safe LPS concentration. The safe incubation condition for the sonosensitizer sinoporphyrin sodium was determined by CCK-8 and fluorometry. An LPS-induced inflammatory model in HL-1 atrial myocytes was used, with experimental groups including control, LPS, LPS+SDT, LPS+sinoporphyrin sodium, and LPS+ultrasound groups. NLRP3 was overexpressed using plasmid transfection, with experimental groups including control, NLRP3 plasmid, negative control plasmid, and NLRP3 plasmid+SDT groups. SDT was applied to LPS-stimulated or NLRP3-overexpressing HL-1 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to measure mRNA and protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Cleaved Caspase-1, IL-1β, IL-18, and CACNA1C. The NLRP3 inhibitor MCC950 was used to validate the relationship of NLRP3 and CACNA1C. The experimental groups included control, LPS, LPS+MCC950, and MCC950 groups. Intracellular reactive oxygen species (ROS) levels were detected using the probe DCFH-DA, and the ROS scavenger N-acetyl-L-cysteine (NAC) was used to test if the effects of SDT was ROS-dependent.Results:(1) In vivo: The LPS+SDT group exhibited a lower incidence of atrial fibrillation induction and a shorter duration of atrial fibrillation compared to the LPS group(both P<0.05). Protein expression levels of NLRP3 and IL-1β were lower than those in the LPS group (all P<0.05), while the expression of CACNA1C subunit tended to increase relative to the LPS group ( P>0.05). (2) In vitro: The safe concentration of LPS for administration was ≤20 μg/ml, with an optimal pro-inflammatory concentration of 4 μg/ml. The safe concentration of sinoporphyrin sodium for administration was 0.4 μmol/L, with an optimal incubation time of 4 hours. Compared to the LPS group or NLRP3 plasmid group, the LPS+SDT group or NLRP3 plasmid+SDT group exhibited lower expression levels of NLRP3, ASC, Cleaved Caspase-1, IL-1β, and IL-18, and higher mRNA and protein levels of CACNA1C (all P<0.05). The LPS+MCC950 group had higher CACNA1C protein expression than the LPS group ( P<0.05). SDT increased intracellular ROS levels, and NAC blocked the regulatory effects of SDT on NLRP3 and CACNA1C. Conclusion:SDT reduces atrial fibrillation susceptibility in mice by inhibiting NLRP3 inflammasome activation in atrial cardiomyocytes, thereby upregulating the L-type calcium channel subunit CACNA1C.

Objective:To evaluate the recurrence and progression of patients with pT1 high grade urothelial carcinoma of bladder (UCB) and glandular differentiation.Methods:We retrospectively analyzed the clinical and pathological information of 208 patients diagnosed as pT1 high grade urothelial carcinoma in the Fifth Central Hospital of Tianjin from January 2006 to February 2019.Among them, 78 cases were diagnosed as glandular differentiation (UCGD), the other 130 patients without histologic variants were served as control. The UCGD group included 62 male and 16 female, whose median age was 67 years old (range 38-81 years old). The control group contained 105 male and 25 female, whose median age was 66 years old (range 40-82 years old). Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate the predictors of oncologic outcomes.Results:The disease recurrence rate and progression rate in UCGD group were 65.4% (51/78) and 28.2% (22/78), higher than 38.5%(50/130) and 14.6%(19/130) of control group ( P<0.05). The median recurrence time in UCGD group was 41 months while 55 months in the control group. The median progression time in UCGD group was 39 months while 54 months in the control group. According to the univariate analysis, largest tumor size ( P=0.030), UCGD ( P=0.003) and lymphovascular invasion (LVI) ( P=0.032) were associated with disease recurrence. UCGD ( P=0.036) and LVI ( P=0.011) were associated with progression. Additionally, Cox multivariate analysis revealed that UCGD ( P=0.001), LVI ( P=0.038) were the independent factors of disease recurrence. UCGD ( P=0.007) and LVI ( P=0.037) were also found to be the independent factors of disease progression. Conclusions:Patients with T1 stage UCB and UCGD are at higher risk of disease recurrence and progression. Therefore, these patients should be followed up closely after being diagnosed and undergo individual treatment according to the situation.

Objective:To evaluate the recurrence and progression of patients with pT1 high grade urothelial carcinoma of bladder (UCB) and glandular differentiation.Methods:We retrospectively analyzed the clinical and pathological information of 208 patients diagnosed as pT1 high grade urothelial carcinoma in the Fifth Central Hospital of Tianjin from January 2006 to February 2019.Among them, 78 cases were diagnosed as glandular differentiation (UCGD), the other 130 patients without histologic variants were served as control. The UCGD group included 62 male and 16 female, whose median age was 67 years old (range 38-81 years old). The control group contained 105 male and 25 female, whose median age was 66 years old (range 40-82 years old). Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate the predictors of oncologic outcomes.Results:The disease recurrence rate and progression rate in UCGD group were 65.4% (51/78) and 28.2% (22/78), higher than 38.5%(50/130) and 14.6%(19/130) of control group ( P<0.05). The median recurrence time in UCGD group was 41 months while 55 months in the control group. The median progression time in UCGD group was 39 months while 54 months in the control group. According to the univariate analysis, largest tumor size ( P=0.030), UCGD ( P=0.003) and lymphovascular invasion (LVI) ( P=0.032) were associated with disease recurrence. UCGD ( P=0.036) and LVI ( P=0.011) were associated with progression. Additionally, Cox multivariate analysis revealed that UCGD ( P=0.001), LVI ( P=0.038) were the independent factors of disease recurrence. UCGD ( P=0.007) and LVI ( P=0.037) were also found to be the independent factors of disease progression. Conclusions:Patients with T1 stage UCB and UCGD are at higher risk of disease recurrence and progression. Therefore, these patients should be followed up closely after being diagnosed and undergo individual treatment according to the situation.

Objective To investigate the effect and mechanism of interleukin (IL)-17C in mice undergoing kidney transplantation. Methods The life-supporting kidney transplantation mice models were established using Balb/c (H-2K^d) mice as the donors, IL-17C gene knock out (IL-17CKO) mice (knockout group) and C57BL/6J(H-2K^b) mice (wild group) were chosen as the recipients. The postoperative body mass and survival time of mice were statistically compared between two groups. Pathological examination of the kidney graft was performed by using hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The expression levels of granzyme B, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6 and IL-1β messenger ribonucleic acid (mRNA) in the kidney graft tissue were quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). The proportion of inflammatory cell infiltration in the kidney graft tissue was detected by flow cytometry. Results In the knockout group, the survival time of mice after kidney transplantation was significantly shorter than that of the wild mice (P=0.031). The body mass was more evidently decreased in the knockout group with no statistical significance from that in the wild group. Pathological examination demonstrated that the kidney graft injury in the knockout group was significantly worse than that in the wild group. The mRNA expression levels of granzyme B, IFN-γ, TNF-α, IL-6 mRNA in the knockout group were significantly up-regulated compared with those in the wild group (all P < 0.01). The mRNA expression level of IL-1β showed a decreasing trend with no statistical significance (P=0.16). Flow cytometry analysis revealed that the infiltration of CD45⁺CD11b⁺Ly6G⁺ neutrophil and CD45⁺CD11b⁺Ly6C^hi monocyte in the kidney graft of knockout mice was significantly higher compared with that of the wild mice (P < 0.05, P < 0.01), whereas the infiltration of CD45⁺Ly6C^hiF4/80⁺ macrophage did not significantly differ between two groups (P > 0.05). Conclusions IL-17C participates in the regulation of inflammatory response after kidney transplantation. It can alleviate acute rejection and improve the survival of kidney graft by down-regulating the expression of pro-inflammatory cytokines and infiltration of inflammatory cells.

Objective To investigate the effects of light acute hypervolemic hemodilution on early postop-erative cognitive function in elderly patients. Methods A total of 60 patients treated by radical surgery were equally randomized to an AHH and a non-AHH control group.Using the Mini-Mental State Examination scale (MMSE),we evaluated the cognitive function of the patients.We made comparisons between the two groups in the plasma S100β levels at T0(before anesthesia induction),T1(immediately after hemodilution),T2(immediately after operating),T(36 hour after operating)and T(424 hour after operating).Results The S-100β lever at T2、T3 and T4were markedly higher than T0in both groups(P<0.05);At T3and T4,the S-100β lever was higher in non-AHH control group than AHH group(P<0.05).There was no significant difference in the incidence of postopera-tive cognitive dysfunction between the two groups(P>0.05)There was no significant difference in the incidence of postoperative cognitive dysfunction between the two groups(P > 0.05). Conclusions AHH can significantly reduce plasma S100β in elderly patients,but there is no effect on early postoperative cognitive function.

ObjectiveTo investigate the role of aldehyde dehydrogenase 2 (ALDH2) in the protection against tubular epithelial cells (TEC) ischemia/reperfusion (IR)injury induced by pretreatment with ethanol.Methods Mouse primary cultured TECs were pretreated with 50 mM ethanol 3 h before simulation of in vitro IR.Lactate dehydrogenase (LDH) release was assessed to evaluate the protection of ethanol pretreatment on IR injury.Thereafter,TECs were transfected with a negative control siRNA (NC) or an ALDH2-siRNA. The ALDH2 protein levels and ALDH enzymatic activities were assessed 48 h after transfection.Ethanol pretreatment and in vitro IR were performed on those transfected TECs.LDH release was assessed to evaluate the role of ALDH2 in the ethanol pretreatment-induced protection against IR injury.ResultsEthanol pretreatment significantly reduced the LDH release in TECs upon IR insult.As compared with NC group and INTERFERin group,the ALDH2 protein levels were decreased by 82.1％,ALDH enzymatic activities were decreased hy 67.3％,and the protective effect induced by ethanol pretreatment was almost completely abrogated in ALDH2-siRNA group.ConclusionEthanol pretreatment protects TECs against IR injury through ALDH2 dependent pathways.