To investigate the regulatory effects of paeonol on autophagy and the NOD-like receptor protein 3 (NLRP3) inflammasome in human renal proximal tubular epithelial cells (HK-2) induced by human serum albumin (HSA).

HK-2 cells were cultured in vitro and randomly assigned to control group, model group, as well as low-, medium- and high-dose experimental groups. Cells in the control group were cultured under normal conditions; those in the model group were treated with 20 mg·mL^-1 HSA for 24 h; and cells in the low-, medium- and high-dose experimental groups were administered 25, 50 and 100 μmol·L^-1 paeonol, respectively, for 24 h on the basis of the model group intervention. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the concentrations of kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), interleukin 1β (IL-1β) and caspase-1 in the cell supernatant. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of KIM-1 and MCP-1. Western blotting was applied to measure the protein expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), interleukin-1β (IL-1β), microtubule-associated protein 1 light chain 3 (LC3), sequestosome 1(p62), Beclin-1, PTEN-induced kinase 1 (PINK1) and Parkin.

The concentrations of KIM-1 in the cell supernatant of the control group, model group, and low-, medium- and high-dose experimental groups were (8.65±0.53), (17.33±2.04), (10.76±1.41), (8.48±0.47) and (8.47±0.24) pg·mL^-1, respectively; the contents of MCP-1 were (531.38±15.64), (2 198.55±148.21), (1 966.29±53.52), (1 605.49±234.68) and (937.33±36.96) pg·mL^-1, respectively; the secretion levels of IL-1β were (71.66±2.29), (109.92±4.41), (91.68±4.75), (80.66±4.00) and (62.38±3.24) pg·mL^-1, respectively; the contents of caspase-1 were (66.57±10.52), (210.50±17.50), (201.88±7.22), (195.42±13.95) and (129.81±13.20) pg·mL^-1, respectively; the relative expression levels of KIM-1 mRNA in each group were 1.05±0.05, 2.38±0.45, 1.58±0.20, 1.44±0.08 and 1.38±0.22, respectively; while those of MCP-1 were 1.04±0.04, 1.53±0.08, 1.32±0.16, 1.16±0.16 and 0.62±0.13, respectively; the relative expression levels of NLRP3 protein were 0.89±0.08, 1.13±0.07, 1.00±0.07, 0.84±0.12 and 0.55±0.16, respectively; those of ASC were 0.23±0.03, 0.87±0.19, 0.81±0.16, 0.78±0.08 and 0.46±0.05, respectively; those of IL-1β were 0.49±0.12, 1.46±0.29, 1.10±0.26, 0.71±0.06 and 0.53±0.13, respectively; the LC3Ⅱ/Ⅰ ratios were 1.08±0.04, 0.90±0.06, 1.00±0.02 and 1.05±0.04, respectively; the expression levels of p62 protein were 0.38±0.06, 1.23±0.11, 1.05±0.20 and 0.62±0.19, respectively; those of Beclin-1 were 0.82±0.07, 0.59±0.06, 0.90±0.07 and 0.93±0.09, respectively; those of PINK1 were 1.10±0.03, 0.68±0.07, 0.78±0.11 and 1.03±0.08, respectively; those of Parkin were 0.64±0.06, 0.46±0.05, 0.58±0.08 and 0.79±0.12, respectively. Compared with the control group, all the above indicators in the model group exhibited statistically significant differences (P<0.05, P<0.01, P<0.001). Moreover, the indicators in the high-dose experimental group showed statistically significant differences compared with the model group (P<0.05, P<0.01, P<0.001).

Paeonol may alleviate albumin-induced renal tubular injury by promoting mitophagy and inhibiting the activation of the NLRP3 inflammasome.

To investigate the impact of quercetin (Que) on myocardial ischemia-reperfusion injury in rats and to elucidate its underlying mechanisms.

A rat model of myocardial ischemia-reperfusion was created by occluding the left anterior descending artery. A total of 60 SD rats were randomly divided into sham group, model group, low-dose experimental group (20 mg·kg^-1 Que), high-dose experimental group (80 mg·kg^-1 Que) and inhibitor group (80 mg·kg^-1 Que+3 mg·kg^-1 MCC950), with 12 rats in each group. Echocardiography was conducted after 14 days of continuous administration to assess the relevant indicators of cardiac function. Rat serum was taken and the amounts of serum myocardial damage indicators and inflammatory factors were detected by kit method. Western blotting was used to determine the relative expression levels of Toll-like receptor 2 (TLR2)/ nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) - related proteins in the rat myocardial tissue.

The left ventricular ejection fraction of rats in sham group, model group, low-dose experimental group, high-dose experimental group and inhibitor group were (79.36±5.37)%, (42.85±3.96)%, (48.51±4.20)%, (71.66±5.14)% and (55.73±4.68)%, respectively; the troponin Ⅰ (cTnⅠ) levels were (0.07±0.01), (0.38±0.03), (0.25±0.03), (0.13±0.01) and (0.20±0.02) ng·mL^-1, respectively; the interleukin-1β (IL-1β) levels were (1.01±0.15), (3.43±0.22), (2.65±0.26), (1.39±0.23) and (1.61±0.13) ng·mL^-1, respectively; the relative expression levels of TLR2 protein were 0.33±0.05, 1.01±0.07, 0.73±0.05, 0.45±0.03 and 0.50±0.06, respectively; the relative expression levels of NLRP3 protein were 0.34±0.06, 1.05±0.09, 0.86±0.07, 0.39±0.06 and 0.56±0.05, respectively. Compared with sham group, the model group showed statistically significant differences in the above indicators (all P<0.05); compared with model group and high-dose experimental group, the low-dose experimental group also exhibited statistically significant differences in the above indicators (all P<0.05).

Quercetin can alleviate myocardial ischemia-reperfusion (I/R) injury in rats and improve cardiac function. The mechanism may be related to the inhibition of the TLR2/NLRP3 inflammatory signaling pathway. Quercetin may exert its cardioprotective effect by down-regulating the expression of TLR2, thereby blocking its activation of the downstream NLRP3 inflammasome, containing NLRP3 and apoptosis-associated speck-like protein containing a CARD (ASC) and ultimately reducing the release of pro-inflammatory factors such as IL-1β.

To observe the clinical efficacy and safety of combining nebulized budesonide suspension with microscopic support laryngoscope cool plasma radiofrequency ablation in the treatment of early glottic carcinoma (EGC).

EGC patients were divided into control group and treatment group based on different treatment regimens. Both groups underwent microscopic support laryngoscope cool plasma radiofrequency ablation. Postoperatively, the control group was administered oral cefaclor extended-release capsules at a dose of 0.5 g per time, twice daily, for 2 consecutive days. The treatment group was given inhaled budesonide suspension at a dosage of 1 mg for nebulization, twice a day, starting one week after surgery, and after one week, switched to nebulization with saline for 3 weeks based on control group. The clinical efficacy, laryngeal morphological indicators, objective voice acoustic indicators, voice disorder index and postoperative follow-up results were compared between the two groups, and conducted a safety assessment.

A total of 98 patients were included, 51 in control group and 47 in treatment group. After treatment, the overall effective rates for control and treatment groups were 84.31% (43 cases/51 cases) and 89.36% (42 cases /47 cases), respectively, with no statistically significant difference (P>0.05). At 4 weeks postoperatively, the morphological scores for the vocal folds in control and treatment groups were (1.45±0.73) and (1.13±0.74) points, respectively; the fundamental frequencies were (168.71±22.58) and (158.02±23.83) Hz, respectively; the frequency perturbations were (0.72±0.11)% and (0.67±0.13)% , respectively; the amplitude perturbations were (4.16±0.56)% and (3.89±0.47)%, respectively; the harmonic-to-noise ratios were (21.39±2.32) and (23.34±2.43) dB, respectively; the physiological scores were (18.45±2.89) and (17.00±3.16) , respectively, with all differences being statistically significant between the two groups (all P<0.05). One case of gastrointestinal reaction occurred in control group; one case of rash and two cases of gastrointestinal reaction occurred in treatment group. The total incidence of adverse drug reactions in treatment and control groups were 6.38% (3 cases/47 cases) and 1.96% (1 case/51 cases), respectively, with no statistically significant difference (P>0.05). The progression-free survival rates for control and treatment groups were 91.30% (42 cases/46 cases) and 95.45% (42 cases /44 cases), respectively, with no statistically significant difference (P>0.05).

Nebulized budesonide budesonide inhalation therapy combined with microscopic support laryngoscope cool plasma radiofrequency ablation provides comparable treatment efficacy to isolated microscopic support laryngoscope cool plasma radiofrequency ablation in patients with EGC, but the former demonstrates more significant improvement in vocal fold morphology and voice quality.

To investigate the potential mechanism of propofol in improving intestinal ischemia-reperfusion injury (IIRI).

SD rats were randomly divided into sham group, model group (the superior mesenteric artery was clamped for 45 min and reperfusion for 2 h), experimental-L group (injection of 30 mg·kg^-1 propofol before ischemia), experimental-M group (injection of 45 mg·kg^-1 propofol before ischemia), experimental-H group (injection of 60 mg·kg^-1 propofol before ischemia); after reperfusion, the rats were killed and intestinal tissues were taken for use. Hematoxylin-eosin (HE) staining was used to observe the intestinal histopathological changes, Western blot assay was used to detect the expression of Bcl-2 antagonist killer(BAK), Bcl-2 associated X(BAX) and other proteins, and real-time quantitative polymerase chain reaction (RT-qPCR) assay was used to detect the expression of cytoplasmic mitochondrial DNA (mtDNA). The enzyme activity and enzyme-linked immunosorbent assay was used to detect the expression of adenosine triphosphate (ATP) and interleukin (IL)-1β in intestinal tissue.

The pathological injury scores (Chiu’s methods) in sham group, model group, experimental-L group, experimental-M group and experimental-H group were (0±0), (4.20±0.60), (3.00±0.45), (2.20±0.40) and (1.00±0.77) points, respectively; the relative expression levels of BAK protein were 0.24±0.03, 0.66±0.08, 0.56±0.08, 0.40±0.05 and 0.34±0.03, respectively; the relative expression levels of BAX protein were 0.35±0.03, 0.79±0.11, 0.62±0.03, 0.51±0.05 and 0.40±0.04, respectively; the relative expression levels of NOD-like receptor pyrin domain-containing protein 3 (NLRP3) protein were 0.32±0.03, 1.05±0.12, 0.81±0.11, 0.64±0.08 and 0.49±0.08, respectively; the relative expression levels of Cyclic guanosine monophosphate adenosine synthase (cGAS) protein were 0.23±0.02, 0.97±0.10, 0.78±0.08, 0.63±0.07 and 0.45±0.07, respectively; the relative expression levels of the NADH dehydrogenase subunit (ND)1 mRNA were 1.00±0.08, 2.23±0.29, 1.79±0.13, 1.59±0.11 and 1.34±0.09, respectively; the levels of ATP production were 1.00±0.14, 0.47±0.03, 0.65±0.07, 0.80±0.06 and 0.81±0.12, respectively. Compared model group with the sham group and compared experimental-L, M, H group with model group, the differences of above indicators were all statistically significant (all P<0.05).

Propofol can dose-dependently improve intestinal injury in IIRI rats and this protective effect was accompanied by downregulation of BAK/BAX protein expression, reduction of mtDNA release, and decreased activity of the downstream cGAS/NLRP3 inflammatory pathway.

To observe the effectiveness and hepatorenal safety of Fule Cream alone or in combination with topical corticosteroids (TCS)/calcineurin inhibitors (TCI) in treating pediatric skin diseases.

Children prescribed Fule cream in our hospital were enrolled and categorized into monotherapy cohort (Fule Cream alone) and combination cohort (Fule cream with TCS/TCI) based on medication use. The changes in liver and kidney function indicators, the incidence of drug-induced liver injury (DILI), acute kidney injury (AKI) and clinical effectiveness were compared between the two cohorts. Outcome variables for effectiveness were constructed by extracting efficacy descriptions from medical record texts.

A total of 2 439 children were included for safety analysis and 741 for effectiveness analysis. Effectiveness analysis showed that the combination cohort had a significantly higher response rate of 77.93% (505 cases/648 cases) than the monotherapy cohort 56.99% (53 cases/93 cases) with an odds ratio (OR) of 0.38 (95% CI: 0.24-0.59). Regarding safety, after treatment, The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in cohort 1 and cohort 2 were significantly decreased after treatment (all P<0.05). The incidence of DILI and AKI was low. Data quality analysis revealed a high missing rate for follow-up laboratory tests and a lack of standardized efficacy evaluations.

The Fule Cream combined with TCS/TCI regimen demonstrated not only superior effectiveness but also no increased clinically significant hepatorenal risk in a real-world setting. Although data missingness may affect the precision of effect estimates, sensitivity analyses support the robustness of the primary conclusions. These findings provide real-world evidence supporting the clinical use of Fule Cream and highlight the necessity of enhancing data governance to generate higher-quality real-world evidence.

To investigate the therapeutic effects and safety of the combination of azithromycin (injection and granules) and montelukast sodium tablets on the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children of different severity.

The children with MPP treated in our hospital were divided into control group and treatment group based on the treatment method. All children received intravenous infusion of azithromycin injection at a dose of 10 mg·kg^-1 qd for 5 days until body temperature returned to normal, followed by oral administration of azithromycin granules at the same dose for 3 days, then 4 days off, for a total course of 3 weeks. On this basis, the treatment group was additionally given montelukast sodium tablets, with a dose of 4 mg·d^-1 for children ≤5 years old, and 5 mg·d^-1 for children over 5 years old, for a total course of 3 weeks. According to the severity of MPP, patients were divided into mild MPP group and severe MPP group. After treatment, the clinical efficacy, NLRP3 inflammasome pathway-related indicators and small airway function indicators were compared between the two groups of children with different severity levels; multiple linear regression was used to analyze the correlation between NLRP3 inflammasome pathway-related indicators and small airway function; and generalized estimating equation (GEE) model was used to analyze the changes in NLRP3 inflammasome pathway-related indicators at different time points, in different groups, and with different severities.

This study included a total of 92 patients, with 46 cases in each group. Confounding factors were adjusted using propensity score matching (PSM), and after matching, 40 cases were included in each group, while 47 cases in mild MPP group and 33 cases in severe MPP group. The white blood cell count (WBC) in severe MPP and mild MPP groups were (10.82±1.59) and (10.06±1.47) ×10⁹·L^-1, C-reactive protein (CRP) were (19.45±8.94) and (8.67±4.08) mg·L^-1, interleukin-6 (IL-6) were (18.25±4.48) and (13.65±4.33) pg·mL^-1, and interleukin-10 (IL-10) were (6.70±1.89) and (5.26±1.35) pg·mL^-1. Comparisons of these indicators between subgroups showed statistically significant differences (all P<0.05). The effective treatment rates of children with mild MPP in treatment group and control group were 100.00% (22 cases/22 cases) and 88.00% (22 cases/25 cases), respectively; the effective treatment rates of children with severe MPP were 88.89% (16 cases/18 cases) and 60.00% (9 cases/15 cases), respectively. Comparisons between groups showed that these differences were statistically significant (all P<0.05). After treatment, the mild and severe MPP children in treatment group had NLRP3 mRNA levels of 0.89±0.11 and 1.11±0.10, apoptosis-associated speck-like protein (ASC) mRNA levels of 0.77±0.10 and 0.95±0.15, caspase-1 mRNA levels of 0.69±0.09 and 0.82±0.10; forced expiratory flow at 25% of the pulmonary volume (FEF25%) levels were (2.72±0.24) and (2.28±0.19) L·s^-1, forced expiratory flow at 50% (FEF50%) levels were (2.90±0.40) and (2.37±0.31) L·s^-1, forced expiratory flow at 75% (FEF75%) levels were (2.13±0.32) and (1.73±0.35) L·s^-1, all showing statistically significant differences (all P<0.05). Correlation analysis showed that in children with MPP, the NLRP3 inflammasome pathway-related indicators NLRP3, ASC and caspase-1 mRNA were all negatively correlated with small airway function indicators FEF25%, FEF50% and FEF75%, and the negative correlations were statistically significant (all P<0.001). GEE results indicated that the reduction in NLRP3 mRNA levels in treatment group was greater than that in control group. In mild MPP, the estimated values for treatment and control groups were -0.76 and -0.56, respectively; the reduction in ASC mRNA in treatment group was greater than in the control group, with estimated values of -0.56 and -0.26, respectively; the reduction in caspase-1 mRNA in treatment group was greater than in control group, with estimated values of -0.32 and -0.26, respectively, and all interaction terms were statistically significant (all P<0.05).

Azithromycin combined with montelukast sodium can significantly improve the clinical efficacy of children with different severity of MPP, reduce the excessive inflammatory response of children with different severity of MPP by targeting and inhibit the NLRP3 inflammasome pathway, and improve the function of the small airway, especially in children with mild disease.

To explore the molecular mechanism by which curcumin (CUR) and chidamide (CHI) synergistically inhibit the malignant behaviors of breast cancer (BC) cells through the interferon (IFN)-retinoic acid-inducible gene Ⅰ (RIG-Ⅰ)-mitochondrial antiviral-signaling protein (MAVS) pathway.

A cellular model was established using MCF-7 breast cancer cells. The cells were divided into five groups: blank group(normol cuttured), CUR group(20 μmol·L^-1 CUR), CHI group(10 μmol·L^-1 CHI), combination group(20 μmol·L^-1 CUR+10 μmol·L^-1 CHI) and inhibitor group(sh-IFN+20 μmol·L^-1 CUR+10 μmol·L^-1 CHI). Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation capacity was evaluated by plate colony formation assay. Cell migration ability was examined using Transwell and wound healing assays. The relative expression levels of apoptosis-related proteins and IFN-RIG-I-MAVS pathway-associated proteins were detected by Western blotting (WB).

Under CUR concentrations of 0, 10, 20 and 40 μmol·L^-1, the half-maximal inhibitory concentrations (IC₅₀) of CHI were (31.48±2.01), (17.57±0.65), (7.56±0.32) and (0.21±0.02) μmol·L^-1, respectively. Statistically significant dose-dependent reductions in IC₅₀ were observed for CHI when combined with 10, 20 and 40 μmol·L^-1 CUR compared to 0 μmol·L^-1 CUR (all P<0.05). The colony formation numbers were (201.28±23.96) cells for the control group, (113.43±15.59) cells for the CUR group, (109.93±11.64) cells for the CHI group, (59.57±6.91) cells for the combination group, and (87.43±5.04) cells for the inhibitor group, respectively; the numbers of invasive cells were (115.03±13.05), (86.51±9.13), (77.82±6.68), (39.54±5.43) and (68.92±3.95) cells, respectively; the wound closure rates were (51.29±5.17)%, (32.80±2.94)%, (31.23±3.10)%, (16.07±2.11)% and (26.94±1.95)%, respectively; the apoptosis rates were (2.21±0.16)%, (12.03±0.85)%, (12.89±0.99)%, (31.62±2.98)% and (16.85±1.04)%, respectively; the relative expression levels of Caspase-3 were 0.38±0.03, 0.55±0.03, 0.52±0.04, 1.12±0.07 and 0.97±0.05, respectively; the relative expression levels of Caspase-9 levels were 0.33±0.02, 0.53±0.02, 0.55±0.04, 1.05±0.06 and 0.60±0.05, respectively; the relative expression levels of Bax levels were 0.34±0.03, 0.52±0.03, 0.53±0.03, 1.08±0.07 and 0.69±0.06, respectively; the relative expression levels of IFN-β levels were 0.33±0.03, 0.46±0.04, 0.53±0.04, 1.09±0.10 and 0.45±0.03, respectively; the relative expression levels of RIG-Ⅰ levels were 0.32±0.02, 0.57±0.05, 0.65±0.04, 1.02±0.11 and 0.59±0.05, respectively; and the relative expression levels of MAVS levels were 0.34±0.02, 0.41±0.03, 0.49±0.04, 1.04±0.12 and 0.51±0.04, respectively. Statistically significant differences were observed when comparing the CUR and CHI groups to the control group, the combination group to the CUR and CHI groups, and the inhibitor group to the combination group (all P<0.05).

CUR enhances the sensitivity of BC cells to CHI and synergistically exerts anti-BC effects with CHI, and its mechanism of action is related to the activation of the IFN-RIG-I-MAVS pathway by CUR.

To evaluate the effects of itraconazole capsules on the pharmacokinetics of a single oral dose of ADC189 and its metabolite ADC189-I07 in Chinese healthy subjects, and to assess the safety of their co-administration.

This was a single-center, open-label, non-randomized, two-period, fixed-sequence trial, using itraconazole as an inhibitor of cytochrome P450 3A4 (CYP3A4), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Analyze the impact of repeated administration of itraconazole capsules on the pharmacokinetic characteristics of ADC189 and its major metabolite ADC189-I07.

After co-administration of ADC189 with itraconazole, there was no difference in the maximum plasma concentration (C_max) of the active metabolite ADC189-I07 in plasma compares with ADC189 alone; the geometric mean ratio was 106.64%, with a 90% confidence interval (CI) of 84.12%-135.16%. The area under the curve (AUC_0-t) and AUC_0-∞ increased by approximately 42.00% and 47.00%, respectively, with geometric mean ratios and 90% confidence intervals of 142.48% (120.84%-167.98%) and 147.25% (123.95%-174.91%), respectively. The 90% CIs for all three parameters did not fall entirely within the no-effect boundary of 80.00%-125.00%. The median time to peak drug concentration (t_max) of ADC189-I07 was 4.00 (3.00-4.00) after administration alone and 4.00 (3.00-12.00) h after co-administration; non-parametric tests showed no statistically significant difference in t_max (P>0.05). All adverse events (AEs) during the trial were grade 1 or 2, resolved spontaneously, and the safety risk was controllable.

When ADC189 tablets are used clinically with a strong CYP3A4 inhibitor, no dosage adjustment is required for concomitant use.