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.

Non-small cell lung cancer(NSCLC)remains the leading cause of cancer-related mortality globally.In recent years,the advent of molecular targeted therapies and immune checkpoint inhibition has profoundly reshaped the therapeutic landscape of NSCLC.As these advanced modalities shift from treating advanced-stage disease toward earlier-stage presentations,perioperative intervention(including neoadjuvant and adjuvant therapy)has risen to the forefront of NSCLC research.To comprehensively address the integration of targeted and immunotherapeutic strategies in the perioperative management of NSCLC research,this review synthesizes the core findings from landmark phase Ⅲrandomized controlled trials such as NeoADAURA and CheckMate 816.Additionally,it presents a succinct summary and analysis of the principal prognostic endpoints used to evaluate perioperative efficacy.Drawing on current evidence related to both efficacy and safety,the review advocates for an individualized precision-oncology approach as a pivotal direction for optimizing perioperative treatment strategies in NSCLC research.

Non-small cell lung cancer(NSCLC)remains the leading cause of cancer-related mortality globally.In recent years,the advent of molecular targeted therapies and immune checkpoint inhibition has profoundly reshaped the therapeutic landscape of NSCLC.As these advanced modalities shift from treating advanced-stage disease toward earlier-stage presentations,perioperative intervention(including neoadjuvant and adjuvant therapy)has risen to the forefront of NSCLC research.To comprehensively address the integration of targeted and immunotherapeutic strategies in the perioperative management of NSCLC research,this review synthesizes the core findings from landmark phase Ⅲrandomized controlled trials such as NeoADAURA and CheckMate 816.Additionally,it presents a succinct summary and analysis of the principal prognostic endpoints used to evaluate perioperative efficacy.Drawing on current evidence related to both efficacy and safety,the review advocates for an individualized precision-oncology approach as a pivotal direction for optimizing perioperative treatment strategies in NSCLC research.

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 explore the effects of peridopril on osteoporosis and possible mechanisms involved.Methods Fifty experimental rats were divided into a normal control group,a sham operation group(Sham group),an ovariectomized group(OVX group),a perindopril group and an estrogen group (E2 group),with ten in each group.The perindopril group was intragastrically administered perindopril 4 mg/kg per day,the E2 group was intragastrically administered estrogen 1.2 mg/kg per day,and rats in the normal control group,the sham group and the OVX group were intragastrically given an equal volume of distilled water.Drugs were given once a day for 12 weeks.After 12 weeks of drug intervention,all rats were anaesthetized and 12 ml blood was extracted from the heart,and serum calcium,phosphorus,alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase(TRACP) were determined by enzyme-linked immunosorbent assays.The bone mineral density(BMD)of the left femur was measured by dual energy X-ray absorptiometry.Results After 4 weeks of drug intervention,the femur BMD was lower in the OVX group than in the sham operation group and the normal control group(F =12.224,P＜0.05),and there was no difference between the sham operation group and the normal control group(P＞0.05).After 12 weeks of drug intervention,serum Ca and P levels had no significant difference between the groups(P＞0.05).ALP and TRACP levels in the OVX group were (192.30± 14.50) U/L and (12.7 ± 1.72) U/L,respectively,which were significantly higher than those in the sham operation group(P＜0.01).ALP and TRACP levels in the perindopril group were (169.00 ± 10.14) U/L and (10.19 ± 1.24) U/L,respectively,which were lower than those in the OVX group(P＜0.05).ALP and TRACP levels in the E2 group were (130.76±9.47) U/L and (7.04±0.96) U/L,respectively,which were lower than those in the OVX group(P＜0.01).BMD in the OVX group was (0.161±0.011) g/cm2,which was lower than that in the sham operation group (P ＜ 0.01).BMD in the perindopril group was (0.173 ± 0.011) g/cm2,which was higher than that in the OVX group(P ＜0.05).After estrogen treatment,BMD of the E2 group was (0.196±0.008) g/cm2,which was higher than that in the OVX group(P ＜0.01).Conclusions Perindopril can decrease high bone turnover,increase bone density in ovariectomized rats,and thus may be used for alleviating postmenopausal osteoporosis.