To observe the efficacy and safety of salmeterol/fluticasone propionate inhalation powder combined with cetirizine oral solution in the treatment of allergic rhinitis (AR) complicated with small airway dysfunction (SAD) in children.

Children with AR and SAD were divided into control group and treatment group using a random number table method. Both groups were given montelukast sodium chewable tablets as basic treatment, taken before bedtime, 4 mg each time, once a day; children in the control group were additionally treated with cetirizine oral solution on the basis of the basic medication, 2.5~10 mL per dose according to age once a day, for 12 consecutive weeks. The treatment group was given salmeterol/fluticasone propionate inhalation powder inhalation powder by oral inhalation on the basis of the control group’s treatment, 1 inhalation each time, twice a day, for 12 consecutive weeks. The clinical efficacy, lung function, eosinophil (Eos) count, inflammatory response indicators, recurrence rate were compared between the two groups, and safety evaluation was conducted.

A total of 83 cases were enrolled, with 39 cases in the control group and 44 cases in the treatment group. After treatment, the total effective rates of the control group and the treatment group were 74.36% (29 cases/39 cases) and 90.91% (40 cases/44 cases), respectively, with statistically significant difference (P<0.05). After treatment, the forced expiratory volume in 1 second (FEV₁) of the control group and the treatment group were 88.75±3.20 and 90.49±3.26, respectively; FEV₁/maximal vital capacity (VC_max) were 89.47±10.83 and 94.57±10.21, respectively; maximal mid-expiratory flow (MMEF) pred were (61.06±6.72)% and (64.39±6.34)%, respectively; Eos counts were (4.81±0.72)% and (4.45±0.68)%, respectively; fraction of exhaled nitric oxide (FeNO) were (24.92±3.30) and (22.86±3.18) ppb, respectively; T-cell immunoglobulin domain and mucin domain protein-1 (Tim-1) were (125.08±20.19) and (113.27±18.06) ng·L^-1, respectively; high mobility group box 1 protein (HMGB1) were (5.12±0.94) and (4.65±0.79) ng·L^-1, respectively, with statistically significant differences (P<0.05, P<0.01). The main adverse drug reactions in the control group were headache, drowsiness, nausea and vomiting, and the main adverse drug reactions in the treatment group were nausea and vomiting, headache and oropharyngeal candidiasis. The total incidence of adverse reactions in the control group and the treatment group were 7.69% (3 cases/39 cases) and 11.36% (5 cases/44 cases), respectively, and the difference was not statistically significant (P>0.05). The recurrence rates of the control group and the treatment group were 33.33% (13 cases/39 cases) and 13.64% (6 cases/44 cases), respectively, with statistically significant difference (P<0.05).

Salmeterol/fluticasone propionate inhalation powder combined with cetirizine oral solution in the treatment of children with AR complicated with SAD can significantly improve efficacy, relieve clinical symptoms, improve lung function, reduce inflammation levels, and has good safety and a low recurrence rate.

To analyze the therapeutic effects and safety of ticagrelor tablets combined with aspirin enteric-coated tablets on young patients with first-onset atherosclerotic acute cerebral infarction.

According to different treatment plans, the patients with first-onset atherosclerotic acute cerebral infarction were divided into the treatment group and the control group. The treatment group was treated with aspirin enteric-coated tablets combined with ticagrelor tablets (initial dose: aspirin enteric-coated tablets 100 mg·d^-1 and ticagrelor tablets 180 mg·d^-1, maintenance dose: aspirin enteric-coated tablets 100 mg·d^-1 and ticagrelor tablets 90 mg·d^-1). The control group was treated with aspirin enteric-coated tablets combined with clopidogrel tablets (initial dose: aspirin enteric-coated tablets 100 mg·d^-1 and clopidogrel tablets 300 mg·d^-1, maintenance dose: aspirin enteric-coated tablets 100 mg·d^-1 and clopidogrel tablets 75 mg·d^-1). The courses of treatment for both groups were 3 months. After 3 months of treatment, the efficacy, National Institutes of Health stroke scale (NIHSS) scores, cerebral hemodynamics, Barthel index, platelet aggregation rate, modified Rankin scale (mRS) scores, adverse cardiovascular events, and adverse reactions were observed.

A total of 103 patients were enrolled, with 53 cases in treatment group and 50 patients in control group. After 3 months of treatment, the total effective rates in the treatment group and the control group were 92.45% (49 cases/53 cases) and 88.00% (44 cases/50 cases), with no statistically significant difference between groups (P>0.05). After 3 months of treatment, the mean blood flow velocities (Vmean) of the middle cerebral artery (MCA) in the treatment group and the control group were (56.73±11.05) and (50.50±10.33) cm·s^-1, respectively; the Vmean of the anterior cerebral artery (ACA) were (45.92±9.83) and (41.28±8.22) cm·s^-1, respectively; the Vmean of the posterior cerebral artery (PCA) were (50.11±10.33) and (45.59±9.12) cm·s^-1, respectively; the Vmean of the vertebral artery (VA) were (52.67±10.49) and (47.81±9.63) cm·s^-1, respectively; the Vmean of basilar artery (BA) were (53.75±10.28) and (48.29±9.60) cm·s^-1, respectively; the platelet aggregation rates were (22.71±7.33)% and (26.47±7.35)%, respectively; the above indexes in the treatment group were significantly different from those in the control group (P<0.05, P<0.01). After 3 months of treatment, the NIHSS scores of the treatment group and the control group were (1.23±0.47) and (1.38±0.49) points, respectively, and the Barthel indexes were (92.17±5.17) and (90.08±6.37) points, respectively. There was no statistically significant difference in the NIHSS score and Barthel index between the treatment group and the control group (all P>0.05). The incidences of adverse cardiovascular events in treatment group and control group were 0% and 8.00% (4 cases/50 cases), respectively, with no statistically significant difference (P>0.05). Adverse drug reactions in the treatment group included gastrointestinal reactions, bleeding tendency, hyperuricemia, and bradycardia, with a total incidence of 13.21% (7 cases/53 cases); adverse drug reactions in the control group included gastrointestinal reactions and bleeding tendency, with a total incidence of 10.00% (5 cases/50 cases); there was no statistically significant difference between groups (P>0.05).

Applying ticagrelor tablets to treat young patients with first-onset atherosclerotic acute cerebral infarction can significantly improve cerebral hemodynamics, with more advantages.

To observe the efficacy of semaglutide injection combined with letrozole tablet in the treatment of obese polycystic ovary syndrome with insulin resistance (PCOS-IR) patients.

Patients with PCOS-IR were divided into treatment group and control group according to the treatment regimen. The control group was administered oral dydrogesterone tablets (10 mg per dose, twice daily) for 14 days to induce withdrawal bleeding. Starting from the 5th day of withdrawal bleeding, letrozole tablets were given orally at a dose of 2.5 mg per day for 5 consecutive days. Two days after drug withdrawal, transvaginal ultrasound monitoring was performed. When the dominant follicle reached or exceeded 18 mm in diameter, human chorionic gonadotropin for injection (1.0×10⁴ U) was intramuscularly injected to induce ovulation. If ovulation did not occur, the dose of letrozole tablets was increased to 7.5 mg per day in the next menstrual cycle. The treatment group received subcutaneous injections of semaglutide (0.25 mg per dose, once weekly for 4 consecutive weeks; starting from the 5th week, the dose was adjusted to 0.5 mg per dose, once weekly for another 8 consecutive weeks). After a 1-week drug withdrawal period (washout period), the same ovulation induction protocol as that for the control group was adopted. Both groups received treatment for 3 to 6 menstrual cycles, and the medication was discontinued immediately once ovulation or pregnancy was achieved. Clinical efficacy, clinical manifestations, reproductive hormone levels, insulin resistance, inflammatory marker levels, follicular development, and the adverse drug reactions were compared between the two groups.

A total of 93 cases were included, with 48 cases in the control group and 45 cases in the treatment group. After treatment, the total effective rates of the control group and the treatment group were 70.83% (34 cases/48 cases) and 88.89% (40 cases/45 cases), respectively; the Rosenfield acne scores were (1.56±0.62) and (1.29±0.59) points, respectively; the Ferriman-Gallwey hair scores were (13.31±3.25) and (11.89±2.85) points, respectively; the follicle-stimulating hormone was (6.86±1.24) and (7.50±1.13) IU·L^-1, respectively; the levels of luteinizing hormone were (8.18±1.52) and (7.48±1.63) IU·L^-1, respectively; the levels of fasting blood glucose (FPG) levels were (4.86±0.97) and (4.36±0.69) mmol·L^-1, respectively; the fasting insulin (FINS) levels were (9.25±1.96) and (8.41±1.87) μIU·mL^-1, respectively; the insulin resistance indexes were 1.83±0.39 and 1.63±0.27, respectively; the vascular endothelial growth factors were (92.17±10.82) and (87.45±10.36) ng·L^-1, respectively; the levels of interleukin-6 were (6.74±0.93) and (6.32±0.99) pg·mL^-1, respectively; the number of follicles were (8.44±1.35) and (7.93±1.01), respectively; the maximum follicle diameters were (11.68±2.44) and (13.05±2.69) mm, respectively; the above indicators in the treatment group were compared with those in the control group and it showed statistically significant differences (all P< 0.05). The total incidences of adverse drug reactions in the experimental group and the control group were 8.89% (4 cases/45 cases) and 10.42% (5 cases/48 cases) (P>0.05).

Semaglutide injection combined with letrozole tablets has significant efficacy in the treatment of PCOS-IR patients, can effectively improve insulin resistance, and has relatively good safety in non-pregnant or non-lactating women.

To evaluate the safety, tolerability, treatment patterns, and effectiveness of calcium polystyrene sulfonate (CPS) and sodium polystyrene sulfonate (SPS) in the management of hyperkalemia (HK) among Chinese patients with renal insufficiency.

Patients with chronic kidney disease (CKD) or acute kidney injury (AKI) with HK in 26 hospitals in China were included in the study. Two full analysis sets (FAS), FAS-P1 (stage 1, followed up for 3 days) and FAS-P2 (stage 2, followed up for 6 months) were defined. Fas-P1 includes all new users taking at least one dose of CPS/SPS 1-3 days after the initial treatment of CPS/SPS, FAS-P2 includes all patients receiving at least one dose of CPS/SPS after enrollment in the user group, and patients receiving at least one dose of CPS/SPS after the initial treatment period in the new user (Fas-P1). The drug use, serum potassium (sK⁺) level and clinical efficacy of the two data sets were observed, and the safety was evaluated.

A total of 892 patients were selected in the study. 390 patients (CPS 385 cases, SPS 5 cases) and 814 patients (CPS 811 cases, SPS 3 cases) were included in FAS-P1 and FAS-P2, respectively. In FAS-P1 and FAS-P2, the average daily doses of CPS were (7.28±6.24) and (5.13±5.15) g, respectively; and the average daily doses of SPS were (10.75±6.23) and (8.36±7.59) g, respectively. In FAS-P1, the change of sK⁺ from baseline to day 3 was (-0.72±0.61) mmol·L^-1; in FAS-P2, the mean value of sK⁺ was (5.17±0.68) mmol·L^-1 (95% CI: 5.12-5.22). In FAS-P1 and FAS-P2, 56.15% and 55.16% patients had adverse events (AEs), respectively, and the incidence of serious adverse events (SAEs) were 29.23% and 29.24%, respectively. The researchers determined that the incidence of adverse events related to CPS/SPS was low, which was 2.56% in FAS-P1 and 2.09% in FAS-P2. The most common CPS/SPS related AEs were gastrointestinal discomfort (FAS-P1: 2.05%; FAS-P2: 1.70/100 person years) and hypokalemia (FAS-P1: 0.51%; FAS-P2: 2.10/100 person years).

In this study, over 50% of patients with renal insufficiency and hyperkalemia experienced AEs, reflecting the high burden of underlying disease in this population. However, the incidence of AEs related to CPS/SPS was low (approximately 2%), predominantly presenting as gastrointestinal discomfort and hypokalemia.

To investigate the efficacy and safety of sintilimab injection combined with S-1 capsules/oxaliplatin injection (SOX) regimen as neoadjuvant therapy for patients with locally advanced gastric cancer (LAGC).

LAGC patients were divided into control group and treatment group based on treatment methods. The control group received neoadjuvant chemotherapy with the SOX regimen, with intravenous infusion of oxaliplatin injection 135 mg·m^-2 on the first day of each cycle, and S-1 capsules were administered orally according to the patient’s body surface area (40 mg each time for <1.25 m², 50 mg each time for 1.25-1.50 m², and 60 mg each time for >1.50 m²), twice a day, for 1-14 days, with every 3 weeks as one cycle. The treatment group received sintilimab injection 200 mg intravenously on the first day of each cycle (every 3 weeks as one cycle) in addition to the control group’s treatment. After both groups completed 4 cycles of treatment, radical gastrectomy+D₂ lymph node dissection was performed. The clinical efficacy, tumor marker levels, safety, and survival status of the two groups were compared.

The control group included 48 cases, and the treatment group included 52 cases. The effective rates of the control group and the treatment group were 52.08% (25 cases/48 cases) and 73.08% (38 cases/52 cases), respectively, After treatment, the levels of carcinoembryonic antigen (CEA) in the control group and the treatment group were (21.08±3.30) and (19.52±2.90) ng·mL^-1, respectively; the levels of carbohydrate antigen (CA) 19-9 were (43.89±5.11) and (41.57±4.73) U·mL^-1, respectively; the levels of CA 72-4 were (24.82±3.15) and (23.18±2.79) U·mL^-1, respectively; the median progression-free survival was 27 and 40 months, respectively; and the median overall survival was 33 and 46 months, respectively. The above indicators of the treatment group were all statistically significantly different from those of the control group (P<0.05, P<0.01). The incidence rates of nausea and vomiting in the control group and the treatment group were 25.00% (12 cases/48 cases) and 15.38% (8 cases/52 cases), respectively; the incidence rates of diarrhea were 14.58% (7 cases/48 cases) and 11.54% (6 cases/52 cases), respectively; the incidence rates of bone marrow suppression were 29.17% (14 cases/48 cases) and 32.69% (17cases/52 caes), respectively, with no statistically significant difference (all P>0.05).

Sintilimab combined with SOX regimen as neoadjuvant therapy for LAGC patients can achieve good clinical efficacy, improve functional status, prolong survival, reduce tumor marker levels, and has fewer surgery-related complications and good safety.

To investigate the clinical efficacy and safety of venetoclax tablet combined with azacitidine for injection in the treatment of newly diagnosed acute myeloid leukemia (AML) patients unsuitable for intensive chemotherapy.

Newly diagnosed AML patients unsuitable for intensive chemotherapy were divided into control group and treatment group based on treatment regimen. The control group received 75 mg·m^-2 azacitidine for injection by subcutaneous injection or intravenous infusion for 7 consecutive days per 28-day cycle. The treatment group received oral venetoclax tablet (dose escalation: 100 mg on day 1, 200 mg on day 2, and 400 mg daily from day 3 onwards) plus 75 mg·m^-2 azacitidine for injection, by subcutaneous injection or intravenous infusion for 7 consecutive days per 28-day cycle. Both groups were treated for 2 cycles. Clinical efficacy, hematological parameters [hemoglobin (Hb), platelet count (PLT), absolute neutrophil count (ANC), white blood cell count (WBC)], bone marrow morphology and cytogenetic assessments (proportion of bone marrow blasts, bone marrow cellularity), liver function indices [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL)], renal function index [serum creatinine (SCr)], coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer], survival outcomes [overall survival (OS), event-free survival (EFS)], and safety indicators were compared between the two groups.

A total of 230 patients were enrolled with 112 in the control group and 118 in the treatment group. After treatment, the overall response rate (ORR) in the treatment group was 74.58% (88 cases/118 cases), significantly higher than the control group’s 53.57% (60 cases/112 cases). The complete remission (CR) rate in the treatment group was 49.15% (58 cases/118 cases), significantly higher than the control group’s 26.79% (30 cases/112 cases); both differences were statistically significant (P<0.05). After treatment, Hb levels of treatment group and control group were (94.85±18.67) and (85.51±17.84) g·L^-1, respectively; PLT counts were (125.51±35.24) ×10⁹·L^-1 and (78.22±29.77) ×10⁹·L^-1, respectively; ANC levels were (4.23±1.87) ×10⁹·L^-1 and (2.79±1.16) ×10⁹·L^-1, respectively; WBC levels were (5.89±2.72) ×10⁹·L^-1 and (6.85±2.73) ×10⁹·L^-1, respectively;. the proportion of bone marrow blasts were (16.90±8.98)% and (29.16±14.18)%, respectively; the proportion of patients with active bone marrow hyperplasia were 80.51% (95 cases/118 cases) and 69.64% (78 cases/112 cases), respectively;. ALT levels were (58.56±25.14) and (45.78±16.57) U·L^-1, respectively; AST levels were (52.34±17.07) and (41.12±17.31) U·L^-1, respectively; TBIL levels were (31.65±12.10) and (25.33±9.12) μmol·L^-1, respectively; SCr levels were (84.32±19.19) and (82.13±17.55) μmol·L^-1, respectively; PT were (14.12±2.42) and (13.78±2.29) s, respectively; APTT were (34.12±5.10) and (33.22±4.65) s, respectively; FIB were (3.56±0.97) and (3.53±0.81) g·L^-1, respectively; D-dimer levels were (0.58±0.22) and (0.52±0.21) mg·L^-1, respectively. Except SCr, PT, APTT, FIB and D-dimer levels, comparion of other indicators between two groups showed statistically significant differences (all P<0.05). The median OS of treatment group and control group were 34.0 and 21.0 months, respectively;, median EFS was 28.0 and 11.0 months. Both median OS and median EFS were significantly longer in the treatment group compared to the control group (both P<0.05). The adverse event (AE) incidence rate was 28.57% (32 cases /112 cases) in the control group and 32.20% (38 cases/118 cases) in the treatment group, with no statistically significant difference (P>0.05).

Venetoclax tablet combined with azacitidine for injection significantly improved the ORR, CR rate, survival outcomes (OS, EFS), hematological recovery, and reduced bone marrow leukemic burden in newly diagnosed AML patients unsuitable for intensive chemotherapy. Although associated with an increased risk of liver toxicity, the overall safety profile was manageable. This combination regimen demonstrates significant clinical value.

To investigate the effect and safety of subanesthetic-dose esketamine combined with subcostal transversus abdominis plane block (STAPB) on postoperative delirium in patients undergoing radical resection for colorectal cancer (CRC).

Patients scheduled for radical CRC resection were divided into control group and treatment group according to the anesthetic regimen. The control group received conventional anesthesia, while the treatment group was intravenously administered 0.2 mg·kg^-1 esketamine hydrochloride injection before endotracheal intubation on the basis of the conventional anesthesia protocol. Both groups underwent STAPB after intubation and before skin incision. The excellent and good rate of anesthesia, surgical parameters, hemodynamic indices, postoperative recovery quality-related indicators, incidence of delirium, analgesic efficacy parameters, and adverse reactions were compared between the two groups.

A total of 52 patients were enrolled in the control group and 48 in the treatment group. The excellent/good rates of anesthesia of treatment group and control group were 91.67% (44 cases/48 cases) and 88.46% (46 cases/52 cases), respectively (P>0.05). The fluid infusion volume of treatment group and control group were (1 412.69±38.27) and (1 428.63±35.47) mL, respectively; the heart rates at T3 were (76.19±8.56) and (80.69±9.14)beats·min^-1, respectively; systolic blood pressure at T3 were (131.08±10.39) and (138.52±13.78) mmHg, respectively; diastolic blood pressure at T3 were (79.94±7.27) and (82.35±8.25) mmHg, respectively; the extubation time were (16.75±2.71) and (15.54±2.42) min, respectively; the recovery time were (18.63±2.81) and (20.40±2.86) min, respectively; the Quality of Recovery-40 (QoR-40) scores on postoperative day 2 were (160.79±18.70) and (154.35±20.56) points, respectively; the lower Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A) on postoperative day 7 were (6.25±1.76) and (7.10±2.05) points, respectively; the Depression subscale (HADS-D) on postoperative day were (6.13±1.82) and (7.15±1.95) points, respectively; the total incidences of delirium were 10.42% (5 cases/48 cases) and 26.92% (14 cases/52 cases), respectively; the Numerical Rating Scale (NRS) scores for resting pain were (2.00±0.41) and (2.17±0.47), respectively; the dynamic pain at 48 h postoperatively were 2.60±0.54 and 2.81±0.60), respectively; the differences of above indicators between two groups were all statistically significant (P<0.05, P<0.01, P<0.001). The main adverse drug reactions included dizziness, tachycardia, bucking, nausea and vomiting in the control group, and dizziness, tachycardia, hypertension, nausea and vomiting in the treatment group. The total incidence of adverse drug reactions was 9.62% (6 cases/52 cases) in the control group and 12.50% (6 cases/48 cases) in the treatment group, with no statistically significant difference (P>0.05).

Subanesthetic-dose esketamine combined with STAPB for patients undergoing radical CRC resection can reduce intraoperative fluid requirements, stabilize perioperative blood pressure and heart rate fluctuations, improve postoperative recovery quality, alleviate postoperative anxiety and depression, and decrease the incidence of postoperative delirium. This combined regimen also yields definite postoperative analgesic effects and does not increase the risk of adverse reactions, thus exhibiting favorable clinical safety and tolerability.

To investigate the distribution patterns of pharmacogenomic characteristics in hypertensive patients treated and to evaluate the differential benefits of genotype-guided therapy in calcium channel blocker (CCB) strategy versus beta-blocker strategy.

In the first phase, pharmacogenomic data of patients with primary hypertension treated at our hospital were analyzed. In the second phase, treatment-naive hypertensive patients were enrolled and randomly assigned in a 1∶1∶1∶1 ratio to four groups: genotype-guided CCB strategy, standard CCB strategy, genotype-guided beta-blocker strategy, and standard beta-blocker strategy. Seven key pharmacogenomic loci, including adrenergic beta-1 receptor (ADRB1) rs1801253 (1165G>C) and cytochrome P450 3A5 (CYP3A5) rs776746, were genotyped using polymerase chain reaction (PCR)-melting curve method. Primary outcomes included time to blood pressure control, incidence of treatment-related adverse events (TRAEs), and length of hospital stay.

In the retrospective phase, 2 783 patients were enrolled. The C allele frequency of ADRB1 rs1801253 was 76.02% (4 231 cases/5 566 cases), and the G allele frequency of CYP3A5*3 was 72.97% (4 062 cases/5 566 cases). In the prospective phase, 300 patients were enrolled. The genotype-guided therapy significantly shortened time to blood pressure control (mean difference: -2.10 days, 95% confidence interval (CI): -2.80 to -1.40, P<0.001), with a significant interaction between therapy approach and treatment strategy (P<0.05). Specifically, in the CCB strategy, genotype-guided therapy reduced control time by 3.20 days (95% CI: -4.10 to -2.30) versus standard therapy, whereas in the beta-blocker strategy, the reduction was only 0.90 days (95% CI: -1.70 to -0.10). Genotype-guided therapy also significantly lowered TRAEs incidence [12.67% (19 cases/150 cases) vs. 25.33% (38 cases/150 cases), P<0.001].

Hypertensive patients at our hospital exhibited a distinct pharmacogenomic profile. Genotype-guided therapy demonstrates substantially greater clinical benefits when applied to CCB strategy than to beta-blocker strategy, providing robust evidence for precision hypertension management within this single-center clinical setting.

To investigate the effect and mechanism of kurarinone on bone marrow-derived macrophages (BMDM) cells through regulating toll-like receptor 9 (TLR9) signaling pathway via cathepsin K (Ctsk).

BMDM cells were divided into control group, model group [receptor activator of nuclear factor-κB ligand (RANKL) 50 ng·mL^-1], kurarinone group (RANKL 50 ng·mL^-1, kurarinone 10 μmol·L^-1), kurarinone+oe-NC group (infected oe-NC, RANKL 50 ng·mL^-1, kurarinone 10 μmol·L^-1), and kurarinone+oe-Ctsk group (infected oe-Ctsk, RANKL 50 ng·mL^-1, kurarinone 10 μmol·L^-1). Quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of Ctsk mRNA; Western blot was used to detect the expression levels of tartrate-resistant acid phosphatase (TRAP) and TLR9 signaling pathway-related proteins; immunofluorescence was used to detect the expression levels of osteoclast differentiation-related proteins; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors; in vitro bone resorption assay was used to detect bone resorption.

The relative expression levels of Ctsk mRNA in the control group, model group, kurarinone group, kurarinone+oe-NC group, and kurarinone+oe-Ctsk group were 1.00±0.15, 2.07±0.28, 1.31±0.18, 1.34±0.14 and 1.79±0.27, respectively; the relative expression levels of TRAP protein were 1.00±0.16, 2.31±0.44, 1.43±0.17, 1.38±0.22 and 1.91±0.30, respectively; the relative fluorescence levels of matrix metalloproteinase-9 (MMP-9) protein were 1.00±0.15, 2.18±0.37, 1.33±0.19, 1.28±0.17 and 1.62±0.31, respectively; the relative fluorescence levels of nuclear factor of activated T-cells 1 (NFATc1) protein were 1.00±0.13, 1.87±0.39, 1.13±0.21, 1.18±0.19 and 1.38±0.22, respectively; the relative fluorescence levels of integrin beta-1 (Itgb1) protein were 1.00±0.19, 1.49±0.25, 1.19±0.22, 1.14±0.17 and 1.32±0.18, respectively; the levels of interleukin-1β (IL-1β) were (15.28±2.05), (44.68±7.93), (31.40±6.08), (33.75±5.76) and (39.62±5.52) pg·mL^-1, respectively; the levels of interleukin-18 (IL-18) were (122.45±22.39), (317.56±51.51), (191.72±33.34), (185.93±32.19) and (217.89±33.58) pg·mL^-1, respectively; the levels of tumor necrosis factor-α (TNF-α) were (81.36±12.27), (216.93±34.39), (130.89±16.18), (125.76±15.15) and (162.94±26.59) pg·mL^-1, respectively; the number of bone resorption pits were (35.26±6.35), (84.72±16.10), (50.38±9.07), (47.85±9.09) and (61.63±10.89) per piece, respectively; the relative area of bone resorption pits were (0.26±0.05)%, (1.38±0.24)%, (1.04±0.18)%, (1.06±0.16)% and (1.27±0.19)%, respectively; the relative expression levels of TLR9 protein were 1.00±0.15, 2.05±0.31, 1.32±0.16, 1.27±0.15 and 1.53±0.24, respectively; the relative expression levels of myeloid differentiation factor 88 (MyD88) protein were 1.00±0.13, 2.18±0.33, 1.42±0.18, 1.36±0.17 and 1.62±0.26, respectively; p-p65/t-p65 were 1.00±0.11, 2.22±0.34, 1.40±0.19, 1.39±0.19, 1.76±0.27, respectively. Compared model group with control group, compared kurarinone group with the model group, compared the kurarinone+oe-Ctsk group with the kurarinone group, the differences of above indicators were all statistically significant (P<0.05, P<0.01, P<0.001).

Kurarinone can inhibit RANKL-induced osteoclast differentiation, inflammatory factor secretion, and bone resorption function by suppressing Ctsk, which may be achieved through inhibiting the TLR9 pathway.

To investigate the effect and mechanism of gastrodin regulating synaptopodin 2 (SYNPO2) on hypoxic-ischemic brain damage (HIBD) in neonatal rats.

The left common carotid artery of neonatal rats was ligated, and the rats were placed in a hypoxic chamber for 40 minutes to establish the HIBD model. Rats were randomly divided into sham operation group (no common carotid artery ligation or hypoxia treatment), model group (HIBD model established), gastrodin group (intraperitoneal injection of gastrodin 100 mg·kg^-1 1 hour before common carotid artery ligation, 1 hour after hypoxia, and 12 hours after hypoxia), gastrodin+oe-NC group (3 days before modeling, 3 microliters oe-NC was transplanted intracerebroventricularly in rats, subsequent treatment same as the gastrodin group) and gastrodin+oe-SYNPO2 group (3 days before modeling, 3 microliters oe-SYNPO2 was transplanted intracerebroventricularly in rats, subsequent treatment same as the gastrodin group), with 10 rats in each group. Western blot was used to detect the levels of SYNPO2 and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling pathway-related proteins; short-term behavioral tests were used to detect neurological function in each group; the dry-wet weight method was used to detect brain water content; TdT-mediated dUTP nick end labeling was used to detect the apoptosis rate of brain tissue cells in each group; immunofluorescence was used to detect the levels of lysosomal associated membrane protein 1 (LAMP1) and microtubule associated protein 1 light chain 3 beta (LC3B) proteins in brain tissue of each group.

The relative expression levels of SYNPO2 protein in the sham operation group, model group, gastrodin group, gastrodin+oe-NC group and gastrodin+oe-SYNPO2 group were 1.00±0.16, 2.05±0.34, 1.38±0.18, 1.35±0.17 and 1.68±0.22, respectively; the relative expression levels of phosphorylated PI3K (p-PI3K)/PI3K protein were 1.00±0.19, 0.25±0.04, 0.65±0.08, 0.68±0.07 and 0.35±0.05, respectively; the relative expression levels of phosphorylated Akt (p-Akt)/Akt protein were 1.00±0.13, 0.28±0.04, 0.49±0.06, 0.51±0.07 and 0.31±0.04, respectively; the relative levels of phosphorylated mTOR (p-mTOR)/mTOR protein were 1.00±0.16, 0.22±0.04, 0.52±0.06, 0.54±0.07 and 0.29±0.05, respectively; the righting reflex latency periods were (2.56±0.33), (14.86±2.12), (5.66±0.75), (5.23±0.79) and (10.33±1.56) s, respectively; the negative geotaxis latency periods were (17.86±2.44), (56.33±8.22), (22.12±3.56), (23.05±3.22) and (40.22±5.66) s, respectively; the cliff avoidance reflex latency periods were (7.11±0.85), (16.55±2.32), (7.22±0.85), (7.83±0.96) and (13.55±2.45) s, respectively; the water contents were (51.56±6.47)%, (62.16±6.22)%, (55.02±6.25)%, (54.63±7.22)% and (61.98±5.17)%, respectively; the apoptosis rates were (5.17±0.65)%, (75.32±9.65)%, (25.65±3.89)%, (23.85±2.98)% and (50.56±6.89)%, respectively; the relative fluorescence intensity of LAMP1 were 1.00±0.15, 3.85±0.44, 1.14±0.15, 1.18±0.19 and 3.22±0.39, respectively; the relative fluorescence intensity of LC3B were 1.00±0.18, 3.45±0.52, 1.25±0.16, 1.21±0.15 and 1.68±0.19, respectively; the above indicators of the model group were statistically significant compared with the sham operation group, the above indicators of the gastrodin group were statistically significant compared with the model group, and the above indicators of the gastrodin+oe-SYNPO2 group were statistically significant compared with the gastrodin+oe-NC group (P<0.05, P<0.01, P<0.001).

Gastrodin inhibits SYNPO2, alleviates brain edema and neurological dysfunction in HIBD rats, protects neuronal structural integrity, reduces neuronal apoptosis, and alleviates excessive autophagy, which may be achieved by activating the PI3K/Akt/mTOR pathway.