To observe the clinical efficacy and safety of evolocumab injection combined with pitavastatin calcium tablets in the treatment of patients with acute coronary syndrome after percutaneous coronary intervention (PCI).

According to cohort method, the patients with acute coronary syndrome after PCI were divided into control group and treatment group. Two groups were treated with routine treatment (anti-platelet, anti-coagulation, reducing myocardial oxygen consumption, improving myocardial ischemia). On the routine treatment, control group was treated with pitavastatin calcium 2 mg per time, once a day, orally before bedtime. On the basis of control group, treatment group was given evolocumab 140 mg per time, once every 2 weeks, subcutaneous injection. Two groups were treated for 6 months. The clinical efficay, blood lipid, myocardial injury indexes, serum levels of amyloid A1 (SAA1) and Gla-rich protein (GRP), major adverse cardiovascular events (MACEs) and safety were compared between two groups.

Fifty-two patients were enrolled in the treatment group and 58 patients were enrolled in the control group. After treatment, the total effective rates of treatment and control groups were 94.23% (49 cases/52 cases) and 75.86% (44 cases/58 cases), and the difference was statistically significant (P<0.05). After treatment, the total cholesterol levels of treatment and control groups were (1.17±0.22) and (1.35±0.25) mmol·L^-1, triglyceride levels were (2.63±0.76) and (3.89±0.92) mmol·L^-1, high-density lipoprotein cholesterol levels were (1.41±0.30) and (1.26±0.28) mmol·L^-1, low-density lipoprotein cholesterol levels were (1.23±0.46) and (1.58±0.55) mmol·L^-1, cardiac troponin I levels were (0.03±0.01) and (0.05±0.02) ng·mL^-1, creatine kinase isoenzyme levels were (12.35±2.38) and (14.23±2.89) U·L^-1, SAA1 levels were (213.92±41.58) and (274.18±43.36) μg·mL^-1, GRP levels were (21.32±3.50) and (19.35±3.27) ng·mL^-1, incidences of MACEs were 9.62% and 24.14%, the differences were statistically significant between two groups (all P<0.05). The adverse drug reactions of two groups were fatigue, pruritus, abdominal pain and elevated aminotransferase. There was no significant difference in total incidences of adverse drug reactions between treatment group and control group (11.54% vs 13.79%, P>0.05).

Evolocumab injection combined with pitavastatin calcium tablets has a definitive clinical efficacy in the treatment of patients with acute coronary syndrome after PCI, which can effectively reduce the blood lipid levels, the incidence of MACEs and myocardial injury, regulate the serum levels of SAA1 and GRP, without increasing the incidence of adverse drug reactions.

To observe the clinical effect and safety of N-acetylcysteine combined with budesonide and terbutaline in the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and respiratory failure (RF).

According to queuing method, patients with AECOPD and RF were divided into treatment group and control group. On basis of basic treatment, control group was given aerosol inhalation of budesonide suspension (1 mg/once, bid) and terbutaline solution (5 mg/once, bid), while treatment group was given aerosol inhalation of N-acetylcysteine solution (0.3 g/once, bid) on basis of control group. All patients were treated for 2 weeks. The clinical effect, pulmonary function indexes [forced vital capacity (FVC), peak expiratory flow (PEF)], dyspnea degree [modified version of British medical research council dyspnea scale (mMRC)], oxidative stress response indexes [superoxide dismutase (SOD)] and inflammatory response indexes [hypersensitive C-reactive protein (hs-CRP)] were compared between the two groups after treatment, and safety was evaluated.

There were 56 cases in control group and 64 cases in treatment group. After treatment, the total effective rate of the treatment group and the control group were 93.75% (60 cases /64 cases) and 82.14% (46 cases /56 cases), respectively, and the difference was statistically significant (P<0.05). After treatment, FVC in treatment group and control group were (2.41±0.59) and (2.08±0.54) L; PEF were (4.97±1.18) and (4.08±1.12) L·s^-1; mMRC scores were (1.86±0.39) and (2.67±0.56) points; SOD levels were (97.54±8.03) and (79.02±7.27) U·L^-1; hs-CRP levels were (5.09±1.42) and (8.63±2.13) mg·L^-1. Compared with control group, the above indexes in treatment group were statistically significant (all P<0.001). The adverse drug reactions in treatment group were mainly on vomiting, rash, palpitation and nausea, while in control group were mainly on fatigue, gastrointestinal reactions and rash. There was no significant difference in total incidence of adverse drug reactions between treatment group and control group [10.94% (7 cases/64 cases) vs 8.93% (5 cases/56 cases), P>0.05].

Curative effect of N-acetylcysteine combined with budesonide and terbutaline is significant in patients with AECOPD and RF, which can promote the recovery of pulmonary function, relieve dyspnea, oxidative stress and inflammatory response.

To analyze the clinical efficacy and safety of salmeterol fluticasone propionate combined with cetirizine hydrochloride and montelukast sodium tablet in the treatment of children with cough variant asthma.

The children with cough variant asthma were divided into control group and treatment group by random number table method. The control group was treated with oral montelukast sodium chewable tablets and cetirizine hydrochloride oral solution, both 10 mg every time, qd; the treatment group was treated with salmeterol fluticasone propionate inhalation powder inhalation, 1 inhalation/time, bid on the basis of the control group. Children in both groups continued treatment for 3 weeks. The clinical efficacy, pulmonary function, airway reaction status, immune function index, inflammatory index and adverse drug reactions were compared between the two groups.

In the treatment group, 50 cases were enrolled, 1 case was lost, and 49 cases were finally included in the statistical analysis. In the control group, 52 cases were enrolled, 3 cases were lost, and finally 49 cases were included in the statistical analysis. After treatment, the total effective rate of the control group and the treatment group were 77.55% (38 cases/49 cases) and 93.88% (46 cases/49 cases), respectively, and the difference were statistically significant (P<0.05). After treatment, the maximum expiratory flow were (4.68±0.56) and (5.07±0.62) L·s^-1 in the control and treatment groups; the vital capacity were (0.98±0.05) and (1.02±0.07) L; the forced expiratory volume in the first second were (75.72±7.24)% and (80.03±8.36)%; the forced vital capacity were (75.49±7.68)% and (79.97±6.72)%; the initial airway resistance were (7.33±0.75) and (7.01±0.73) cm H₂O·L^-1·s^-1; the minimum induced cumulative dose were (1.89±0.14) and (2.01 ± 0.25) mg·L^-1; the 35th percentile of specific airway conduction decrease were (5.24±0.52)% and (5.59±0.68)%. There were statistically significant differences in the above indexes between the treatment group and the control group (P<0.05, P<0.01, P<0.001). The adverse drug reactions of the control group and the treatment group were headache, palpitation and sleep difficulty, and the incidence of the total adverse drug reactions of the treatment group and the control group were 6.12% (3 cases /49 cases) and 12.24% (6 cases /49 cases), respectively, with no statistical significance (P>0.05).

Salmeterol fluticasone propionate, cetirizine hydrochloride and montelukast sodium tablet are effective and safe in the treatment of children with cough variant asthma.

To observe the clinical efficacy of nilapalil toluene sulfonate capsules, bevacizumab injection, and their combination therapy for ovarian cancer, and to assess their impact on serum biomarkers and ovarian blood flow parameters.

Ovarian cancer patients were divided into three groups according to a cohort methods: Control A group, control B group, and combined group. Control A group received nilapalil toluene sulfonate capsules, 300 mg once daily for 21 days per cycle. Control B group received bevacizumab injection 7.5 mg·kg^-1, administered every 3 days for 21 days per cycle. The combined group received both nilapalil toluene sulfonate capsules and bevacizumab injection following the same regimen as the control groups. All groups underwent 4 cycles of treatment. Clinical efficacy, serum tumor biomarkers, ovarian blood flow parameters, adverse drug reactions, and patient survival were compared across the three groups.

A total of 31 patients in control A group, 28 patients in control B group, and 41 patients in the combined group were included. After treatment, the total effective rates for control A group, control B group, and the combined group were 70.97% (22 cases/31 cases), 71.43% (20 cases /28 cases) and 92.68% (38 cases /41 cases), respectively. The combined group showed a significantly higher effective rate compared to both control A group and control B group (all P<0.05). After treatment, the serum levels of carcinoembryonic antigen (CEA) in control A group, control B group, and the combined group were (15.26±2.33), (14.89±2.34) and (9.74±1.21) μg·L^-1, respectively; and the pulsatility index (PI) were 1.35±0.24, 1.39±0.21 and 1.82±0.32, respectively. The combined group showed significant differences in these parameters compared to both control A group and control B group (all P<0.05). Adverse drug reactions in control A group mainly included gastrointestinal reactions, hair loss, and proteinuria; control B group had gastrointestinal reactions, hair loss, and muscle pain; and the combined group experienced gastrointestinal reactions, hair loss, proteinuria, and muscle pain. The overall adverse drug reaction rates in control A group, control B group, and the combined group were 25.81% (8 cases /31 cases), 25.00% (7 cases /28 cases) and 26.38% (11 cases /41 cases), respectively, with no significant difference between the groups (all P>0.05). After 12 months of follow-up, the survival rates for control A group, control B group, and the combined group were 70.97% (22 cases /31 cases), 67.86% (19 cases /28 cases) and 90.24% (37 cases /41 cases), respectively. The survival rate of the combined group was significantly higher than that of control A group and control B group (all P<0.05).

The combination of nilapalil toluene sulfonate capsules and bevacizumab injection in the treatment of ovarian cancer effectively reduces serum biomarker levels, improves ovarian blood flow parameters, has a low incidence of adverse drug reactions, high safety, and significantly improves patient survival.

To observe the effect and safety of dydrogesterone combined with estradiol valerate on preventing the intrauterine re-adhesion after intrauterine adhesion (IUA) surgery.

The patients after IUA surgery were divided into control group and treatment group according to the cohort method. The control group was given oral estradiol valerate tablets (2 mg every time, twice a day) immediately after surgery and stopped after 30 days of continuous oral administration, and on the basis of the control group; the treatment group received dydrogesterone tablets (10 mg each time, once a day) from the 20^th day until the next menstruation. Both groups were treated for 2 menstrual cycles. The efficacy, endometrial receptivity ultrasound parameters [endometrial thickness, endometrial volume, vascular index (VI), blood flow index (FI), vascular blood flow index (VFI)], sex hormones [estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH)], adverse reactions and occurrence of re-adhesion were compared between the two groups.

Forty-eight cases in treatment group and 44 cases in control group were finally included. After 2 menstrual cycles of treatment, the total effective rates in treatment group and control group were 95.83% (46 cases/48 cases) and 81.82% (36 cases/44 cases), respectively (P<0.05). After 2 menstrual cycles of treatment, the endometrial thicknesses in treatment group and control group were (7.88±1.02) and (7.12±0.86) mm; the endometrial volumes were (3.02±0.97) and (2.57±0.73) cm³; VI values were 1.21±0.59 and 0.88±0.57; FI values were 29.87±5.12 and 27.56±4.63; VFI values were 1.12±0.43 and 0.83±0.36; E2 levels were (239.62±25.47) and (168.91±20.12) pmol·L^-1; FSH levels were (8.94±2.02) and (10.63±2.14) U·L^-1; LH levels were (13.38±2.16) and (15.27±2.59) U·L^-1, respectively (all P<0.05). The adverse drug reactions in treatment group were mainly breast tenderness and digestive tract discomfort; and the adverse drug reactions in control group were mainly breast tenderness, digestive tract discomfort and headache. The total incidence rates of adverse drug reactions in treatment group and control group were 14.58% (7 cases/48 cases) and 11.36% (5 cases/44 cases), respectively (P>0.05). The incidence rates of re-adhesion in treatment group and control group were 6.25% (3 cases/48 cases) and 20.45% (9 cases/44 cases) (P<0.05).

Dydrogesterone combined with estradiol valerate has a significant effect on preventing intrauterine re-adhesion after IUA surgery, and it can effectively improve the endometrial receptivity and sex hormones levels of patients, and it has medication safety.

To observe the anesthetic effects and safety of remazolam injection combined with alfentanil injection in the treatment of patients with hysteroscopic surgery.

Patients scheduled for hysteroscopic surgery were randomly divided into control group and treatment group. The control group received intravenous 1.5-2.0 mg·kg^-1 propofol + 7-10 μg·kg^-1 alfentanil for anesthetic induction, during the surgery, continuously infused with 4-12 mg·kg^-1·h^-1 propofol + 0.05-0.20 μg·kg^-1·h^-1 remifentanil for anesthesia maintenance. The treatment group was given intravenous 0.3-0.5 mg·kg^-1 remimazolam + 7-10 μg·kg^-1 alfentanil for anesthetic induction, during the surgery, received 0.5-1.0 mg·kg^-1·h^-1remazolam+ 0.05-0.20 μg·kg^-1·h^-1 remifentanil for anesthesia maintenance. The hemodynamics, analgesic effects, cognitive function and safety were compared between the two groups.

Control group were enrolled 52 cases, 3 cases dropped out, and 49 cases were finally included in the statistical analysis. Treatment group were enrolled 53 cases, 4 cases dropped out, and 49 cases were finally included in the statistical analysis. At the end of the surgery, the mean arterial pressure of treatment and control groups were (73.98±7.41) and (60.10±6.84) mmHg, the heart rates were (68.43±7.32) and (63.92±7.36) beat·min^-1, the differences of above index were statistically significant between two groups (all P<0.05). One hour after operation, the visual analogue scale scores of treatment and control groups were (3.08±0.49) and (3.86±0.61) points, the mini-mental state examination scores were (22.65±2.41) and (18.24±2.38) points, the differences were statistically significant (all P<0.05). The adverse drug reactions of treatment group were nausea, while those in the control group were bradycardia, hypotension, respiratory depression and nausea. The total incidences of adverse drug reactions in the treatment and control groups were 2.04% and 14.29%, with statistically significant difference (P<0.05).

Remazolam injection combined with alfentanil injection can help to maintain hemodynamics of patients with hysteroscopic surgery, reduce the risk of postoperative pain and cognitive impairment, with good safety.

To observe the influence of propofol injection emulsion combined with esketamine injection on hemodynamics and postoperative recovery quality in elderly patients after lower limb arthroplasty.

The elderly patients undergoing lower limb joint replacement were divided into low-dose group (0.25 mg·kg^-1 esketamine), high-dose group (0.50 mg·kg^-1 esketamine) and control group (equal volume of 0.9% NaCl) according to the cohort method. Hemodynamics [heart rate (HR), mean arterial pressure (MAP)], postoperative recovery quality scale-15 (QoR-15) scores, dosages of anesthetic drugs, Ramsay sedation score, recovery quality and adverse reactions were compared among the three groups.

In this study, 39 cases were enrolled in the low-dose group, 40 cases in the high-dose group and 42 cases in the control group. The HR of patients in low-dose group, high-dose group and control group immediately after operation (T1) was (76.39±5.77), (77.16±5.24) and (73.21±4.79) beat·min^-1, respectively; MAP values were (85.11±5.22), (85.21±5.37) and (82.79±4.86) mmHg, respectively; at 15 min after operation, the HR of T2 were (78.36±5.11), (78.24±5.02) and (80.67±4.57) beat·min^-1; the MAP were (85.75±5.11), (85.39±4.97) and (87.93±3.67) mmHg, respectively; the QoR-15 scores 24 h after operation were (108.19±10.29), (109.56±10.12) and (99.66±10.21) points, respectively; the dosage of propofol were (220.66±25.19), (211.66±27.88) and (283.37±26.28) mg, respectively; the dosage of remifentanil were (2.37±0.42), (2.24±0.38) and (2.89±0.35) mg, respectively; Ramsay sedation scores were (1.56±0.27), (1.61±0.22) and (1.58±0.24) points at T0; and (3.18±0.33), (3.29±0.34) and (2.67±0.29) points at T3, respectively. Compared with the control group, there were statistically significant differences in the above indexes between the low-dose group and the high-dose group (all P<0.05), while there were no statistically significant differences in the above indexes between the low-dose group and the high-dose group (all P>0.05). Adverse drug reactions included respiratory depression, nausea/vomiting, dizziness, restlessness, hypotension, etc. The total incidence of adverse drug reactions were 2.56% (1 case /39 cases) in the low-dose group, 15.00% (6 cases/40 cases) in the high-dose group, and 26.19% (11 cases /42 cases) in the control group. The total incidence of adverse drug reactions of low-dose group was significantly lower than the control group, and the difference was statistically significant (P<0.05).

The application of propofol combined with esketamine can reduce the intraoperative dosages of propofol and remifentanil in elderly patients undergoing knee arthroplasty, enhance the sedation effect, improve the hemodynamics, and promote the postoperative recovery.

To investigate the clinical effect of cinacalcet in the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing hemodialysis for chronic kidney disease (CKD).

Patients who underwent hemodialysis for CKD and had SHPT were divided into the control group and the treatment group according to the cohort method. The control group was treated with 0.25 μg of calcitriol capsules once a day via oral administration. On this basis, the treatment group was treated with 25 mg of cinacalcet tablets once a day via oral administration. Patients in both groups were treated for 12 weeks. Clinical efficacy, parathyroid volume, parathyroid function [serum phosphorus, serum calcium, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH)], and cardiovascular function [creatine kinase-MB (CK-MB), hypersensitive troponin Ⅰ (hs-cTnⅠ) and myoglobin (MYO)]were compared between the two groups. Safety was evaluated.

Sixty-two cases were enrolled in the treatment group and fifty-eight cases in the control group. After treatment, the total effective rates in the treatment group and the control group were 93.55% (58 cases/62 cases) and 77.59% (45 cases/58 cases), with statistically significant difference (P<0.05). After treatment, serum phosphorus levels in the treatment group and the control group were (1.31±0.16) and (1.50±0.34) mmol·L^-1; serum calcium levels were (2.63±0.91) and (2.25±0.72) mmol·L^-1; ALP levels were (83.28±8.40) and (126.46±12.39) U·L^-1; iPTH levels were (215.32±16.69) and (307.65±20.14) pg·mL^-1. The differences were statistically significant (all P<0.05). After treatment, the length of the parathyroid gland in the treatment group and the control group were (0.58±0.10) and (0.77±0.19) cm; width were (0.34±0.08) and (0.45±0.16) cm; thickness were (0.25±0.05) and (0.33±0.15) cm; volume were (0.82±0.15) and (1.13±0.22) cm³. The differences were statistically significant (all P<0.05). After treatment, serum CK-MB levels in the treatment group and the control group were (4.18±0.73) and (6.53±1.26) ng·mL^-1; hs-cTnⅠ levels were (0.04±0.01) and (0.07±0.03) ng·mL^-1; MYO levels were (70.69±9.41) and (112.39±12.60) ng·mL^-1. The differences were statistically significant (all P<0.05). The adverse drug reactions in the treatment group and the control group mainly included nausea and vomiting, increased blood pressure, and myalgia. The total incidence of adverse drug reactions in the treatment group and the control group were 8.06 % (5 cases / 62 cases) and 22.41% (13 cases / 58 cases), respectively, and the difference was statistically significant (P<0.05).

Cinacalcet is effective in the treatment of SHPT in patients undergoing hemodialysis for CKD. It can reduce parathyroid gland volume, maintain calcium and phosphorus metabolism, and protect cardiovascular function, with high safety.

To observe the clinical efficacy and safety of recombinant epidermal growth factor (rhEGF) gel combined with gelatin sponge application under ear endoscopy in the treatment of traumatic tympanic membrane perforations.

Patients with traumatic tympanic membrane perforations were divided into control group and treatment group using cohort method. The control group received intravenous infusion of clindamycin phosphate injection (0.9 g, once daily). The treatment group received rhEGF gel (1 drop per dose, twice daily) combined with gelatin sponge application under ear endoscopy. Both groups received treatment for 1 week. The clinical efficacy, inflammatory markers [white blood cell count (WBC), C-reactive protein (CRP)], hearing status, and safety were compared between the two groups.

A total of 37 patients in the control group and 43 patients in the treatment group were enrolled. The overall treatment efficacy in the treatment and control groups were 95.35% (41 cases /43 cases) and 78.38% (29 cases/37 cases), respectively, with statistically significant difference (P<0.05). After treatment, the WBC levels in the treatment and control groups were (7.74±1.47) and (10.68±1.64) × 10·L^-1, respectively; the CRP levels were (3.37±0.97) and (6.35±1.01) pg·mL^-1, respectively; the air conduction hearing thresholds were (25.64±2.13) and (29.68±2.24) dB HL, respectively; and the air-bone conduction gap were (6.54±1.24) and (12.36±2.47) dB, respectively. The treatment group showed statistically significant differences in all these indicators compared to the control group (all P<0.05). The adverse drug reactions in the treatment group, the main adverse drug reaction was infection, while in the control group mainly included infection and re-perforation. The incidence of adverse drug reactions in the treatment and control groups were 4.65% (2 cases /43 cases) and 10.81% (4 cases /37 cases), respectively, with no significant difference (P>0.05).

The clinical efficacy of treating patients with traumatic tympanic membrane perforation by combining rhEGF gel with absorbable gelatin sponge patch is better than that of conservative treatment. It has a low incidence of adverse drug reactions and high safety.

To evaluate the in vitro antibacterial activity of cefteram against common clinically isolated bacteria in the past three years.

The clinical isolates were collected and the minimal inhibitory concentration (MICs) were determined by the microdilution method.

A total of 484 pathogenic bacteria over the period 2021-2023 were studied. The results show that cefteram has good antibacterial activity against Streptococcus spp other than penicillin-resistant Streptococcus pneumoniae (MICs of penicillin ≥ 2 mg·L^-1), MIC₉₀ value of cefteram was less than or equal 1 mg·L^-1, and the susceptibility rate was 100.0%, which was similar to penicillin, slightly better than cefpodoxime, better than cefuroxime, cefixime, cefaclor and cefalexin. Against gram-negative bacteria, cefteram also showed better antibacterial activity, especially against β-lactamase (ESBLs) negative Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Haemophilus influenzae, and Moraxella catarrhalis. The MIC₉₀ value of cefteram was ≤ 2 mg·L^-1, and the susceptibility rate was 100.0%. Especially for Hemophilus influenzae, cefteram was better than all comparator agents, were comparable to cefpodoxime, better than cefuroxime, cefaclor and cefalexin. For Peptostreptococcus spp., cefteram was comparable to cefuroxime, better than all compared agents.

Cefteram had a wide and balanced antibacterial against clinical isolatied of gram-negative bacteria, gram-positive bacteria and anaerobic bacteria in China in recent years. Cefteram also showed better antibacterial activity, especially against penicillin intermediate and ampicillin-resistant Hemophilus influenzae, and is a good variety among oral cephalosporins.

To investigate the effect and mechanism of ursodeoxycholic acid on bronchial epithelial cell injury induced by toluene diisocyanate (TDI).

BEAS-2B cells were randomly divided into control group (conventional culture), TDI-human serum albumin (HSA) group (120.00 mg·L^-1 TDI-HSA), low-dose group (100 μmol·L^-1 ursodeoxycholic acid+120.00 mg·L^-1 TDI-HSA), high-dose group (200 μmol·L^-1 ursodeoxycholic acid+120.00 mg·L^-1 TDI-HSA) and rapamycin group (25 nmol·L^-1 rapamycin+120.00 mg·L^-1 TDI-HSA). The expression of inflammatory factors was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA); the level of reactive oxygen species (ROS) was detected by DCFH-DA; and the protein expression of each cell was detected by Western blot.

The mRNA levels of interleukin (IL)-6 in control group, TDI-HSA group, low-dose group and high-dose group were 1.00±0.13, 2.20±0.24, 1.87±0.12, 1.48±0.14, respectively; IL-8 levels were (22.65±1.96), (81.42±6.35), (56.36±5.88), (38.28±3.25) pg·mL^-1, respectively; ROS levels were (100.00±3.47)%, (351.25±22.52)%, (312.80±26.59)%, (242.15±13.60)%, respectively; the protein levels of dynamic associated protein 1 (DRP1) were 0.23±0.03, 0.82±0.08, 0.69±0.10, 0.55±0.05, respectively; benzyl chloride 1 (Beclin1) protein expression levels were 0.23±0.04, 0.60±0.07, 0.44±0.04, 0.37±0.03, respectively; phosphorylated adenylate activates protein kinase (p-AMPK) protein expression levels were 0.20±0.05, 0.49±0.05, 0.40±0.03, 0.34±0.04, respectively. Beclin1 protein expression levels in high-dose group and rapamycin group were 0.35±0.04 and 0.69±0.07, respectively; IL-6 levels were (17.63±1.36) and (29.52±3.49) pg·mL^-1, respectively; IL-18 levels were (65.22±5.30) and (95.58±6.80) pg·mL^-1, respectively. The above indexes: TDI-HSA group was compared with control group, low- dose group and high- dose group were compared with TDI-HSA group, rapamycin group compared with high dose group, the differences were significant (all P<0.05).

Ursodeoxycholic acid may mediate ROS/AMPK/ autophagy pathway to improve the inflammatory response and mitochondrial dysfunction induced by TDI-HSA.

To investigate the effects of almonertinib on the proliferation, invasion, epithelial-mesenchymal transition (EMT), and stemness of non-small-cell lung cancer (NSCLC) cells by regulating microRNA-22 (miR-22) targeting ubiquitin-conjugating enzyme E2O (UBE2O).

Human lung adenocarcinoma cell line NCI-H1975 was randomly divided into control group (normal culture with no treatment), medium-dose group (4 μmol·L^-1 almonertinib), inhibitor negative control (NC inhibitor) group (4 μmol·L^-1 almonertinib + miR-22 inhibition negative control), miR-22 inhibitor group (4 μmol·L^-1 almonertinib + miR-22 inhibition), miR-22 inhibitor+short hairpin negative control (sh-NC) group (4 μmol·L^-1 almonertinib + miR-22 inhibition + short hairpin negative control), and miR-22 inhibitor+short hairpin UBE2O (sh-UBE2O) group (4 μmol·L^-1 almonertinib + miR-22 inhibition + short hairpin UBE2O). The expression of miR-22 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) ; Western blot analysis was performed to detect the expression of octamer-binding transcription factor 4 (OCT4), SRY-Box transcription factor 2 (SOX2), and Nanog; the cell proliferation rate was assessed using the 5-ethynyl-2-deoxyuridine (EdU) assay; and Transwell assays were conducted to evaluate cell invasion ability.

The expression levels of miR-22 in the control group, medium-dose group were 1.00±0.16, 2.07±0.34. The expression levels of OCT4 in the control group, medium-dose group, NC inhibitor group, and miR-22 inhibitor group were 1.00±0.16, 0.63±0.09, 0.67±0.08 and 0.94±0.12, respectively; SOX2 expression levels were 1.00±0.14, 0.48±0.06, 0.54±0.07 and 0.81±0.11; and Nanog expression levels were 1.00±0.18, 0.45±0.08, 0.52±0.11 and 0.89±0.15. The cell proliferation rates in the control group, medium-dose group, NC inhibitor group, miR-22 inhibitor group, miR-22 inhibitor+sh-NC group, and miR-22 inhibitor+sh-UBE2O group were (87.29±10.73)%, (41.65±7.82)%, (48.47±6.54)%, (79.31±10.26)%, (84.50±11.98)% and (36.82±6.79)%, respectively. The numbers of invading cells were (156.92±24.81), (72.53±9.06), (64.41±10.75), (143.27±26.19), (137.58±21.46) and (75.23±11.94), respectively. Compared between the control group and medium-dose group, NC inhibitor and miR-22 inhibitor groups, as well as miR-22 inhibitor+sh-NC and miR-22 inhibitor+sh-UBE2O groups showed statistically significant differences (all P<0.05).

Almonertinib can inhibit the proliferation and invasion of NSCLC NCI-H1975 cells, likely by regulating miR-22 to target UBE2O.

To investigate the effects of circCSPP1 mediated autophagy on the proliferation and metastasis ability of gastric cancer cells.

The human gastric cancer cells NCI-N87 were divided into Vector group (transfected with Vector), circCSPP1 group (transfected with circCSPP1) and inhibitor group (transfected with circCSPP1 and incubated with 10 μmol·L^-1 chloroquine). The MKN-45 cells were divided into sh-NC group (transfected with circCSPP1 shRNA-NC), sh-circCSPP1 group (transfected with circCSPP1 shRNA) and agonist group (transfected with circCSPP1 shRNA + 1 μmol·L^-1 sirolimus). Flow cytometry was used to detect cell apoptosis. Transwell was used to detect cell migration and invasion. Western blot were used to detect the expression levels of microtubule associated protein light chain 3-Ⅱ (LC3-Ⅱ) and p62 protein.

In NCI-N87 cells: the apoptosis rates of Vector, circCSPP1 and inhibitor groups were (7.95±0.66)%, (3.93±0.62)% and (7.37±0.85)%; the number of cell migrations were 122.50±12.25, 169.40±16.09 and 109.00±8.22; the number of cell invasions were 73.38±12.33, 117.30±12.78 and 55.25±8.73; the relative expression levels of LC3-Ⅱ protein were 0.40±0.06, 1.13±0.11 and 0.44±0.08; the relative expression levels of p62 protein were 1.62±0.15, 0.21±0.08 and 1.43±0.16. The differences of above indexes were statistically significant between the circCSPP1 group and the inhibitor and Vector groups (all P<0.05). In MKN-45 cells: the cell apoptosis rates of sh-NC, sh-circCSPP1 and agonist groups were (6.81±0.68)%, (12.02±0.78)% and (5.76±1.21)%; the number of cell migrations were 191.60±21.43, 87.50±10.76 and 155.60±10.36; the number of cell invasions were 150.00±11.55, 61.63±11.39 and 154.50±17.99; the relative expression levels of LC3-Ⅱ protein were 1.08±0.05, 0.13±0.03 and 1.18±0.06; the relative expression levels of p62 protein were 0.15±0.03, 1.29±0.08 and 0.19±0.04. Compared with the sh-circCSPP1 group, the differences of above indicators in the agonist and sh-NC groups were statistically significant (all P<0.05).

circCSPP1 can improve the proliferation and metastasis ability of gastric cancer cells by inducing autophagy.

To investigate the effect of microRNA-183-5p (miR-183-5p) targeting RNA-binding motif single-stranded-interacting protein 1 (RBMS1) on autophagy and migration of breast cancer cells and its mechanism.

Human breast cancer cells MCF-7 were divided into control group, NC inhibitor group (transfected with NC inhibitor) and miR-183-5p inhibitor group (transfected with miR-183-5p inhibitor), miR-183-5p inhibitor+si-NC group (transfected with miR-183-5p inhibitor and empty vector si-NC), miR-183-5p inhibitor+si-RBMS1 group (transfected with miR-183-5p inhibitor and RBMS1 knockdown plasmid si-RBMS1). The expression levels of autophagy and phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathway-related proteins in each group were detected by Western blot, and the mobility of cells in each group was detected by scratch test.

Control group, NC inhibitor group, miR-183-5p inhibitor group, miR-183-5p inhibitor+si-NC group and miR-183-5p inhibitor+si-RBMS1 group the relative expression levels of light chain 3 Ⅱ (LC3-Ⅱ)/light chain 3 Ⅰ (LC3-Ⅰ) protein were 0.29±0.03, 0.31±0.03, 0.86±0.10, 0.84±0.09 and 0.43±0.05, respectively; the relative expression levels of Beclin-1 protein were 0.18±0.02, 0.20±0.02, 0.74±0.08, 0.78±0.09 and 0.35±0.04, respectively; the relative expression levels of sequestosome-1 (P62) protein were 0.93±0.12, 0.89±0.10, 0.51±0.06, 0.54±0.06 and 0.86±0.10, respectively; the 48 h cell mobility was (62.87±7.26)%, (59.23±6.89)%, (24.13±3.49)%, (26.14±4.72)% and (40.11±5.71)%, respectively; the relative expression levels of phospho- (p-) PI3K/PI3K protein were 0.67±0.12, 0.64±0.10, 0.32±0.06, 0.35±0.06 and 0.74±0.09, respectively. The above indexes of miR-183-5p inhibitor+si-RBMS1 group were compared with those of miR-183-5p inhibitor+si-NC group, and those of miR-183-5p inhibitor group were compared with those of NC inhibitor group, and the differences were statistically significant (all P<0.05).

Inhibition of miR-183-5p expression can promote autophagy and inhibit cell migration in MCF-7 cells, while down-regulation of RBMS1 has the opposite effect, which is related to the PI3K/Akt/mTOR pathway.

To investigate the regulatory effects of aloperin on bladder cancer cell growth and endoplasmic reticulum stress-dependent mitochondrial pathway.

253J cells were randomly divided into control group, experimental-L group (25.0 μmoL·L^-1 aloperin), experimental-M group (50.0 μmoL·L^-1 aloperin), experimental-H group (100.0 μmoL·L^-1 aloperin), 4-PBA group [100.0 μmoL·L^-1 aloperin+20 μmoL·L^-1 4-phenylbutyric acid (4-PBA)], si-NC (transfected with si-NC+100.0 μmoL·L^-1 aloperin), si-CHOP group [transfected with si-CCAAT-enhancer-binding protein homologous protein (CHOP)+100.0 μmoL·L^-1 aloperin]. Cell proliferation was detected by 5-ethynyl-2′-deoxyuridine (EdU) assay; protein expression was detected by Western blot assay; apoptosis was detected by flow cytometry; mitochondrial membrane potential (MMP) was detected by JC-1 assay.

The EdU positive cell rates in control group, experimental-L group, experimental-M group and experimental-H group were (37.51±2.98)%, (29.52±2.19)%, (23.10±2.58)% and (12.94±2.52)%, respectively; the expression levels of C/EBP homologous protein (CHOP) were 0.29±0.04, 0.53±0.05, 0.71±0.08, 0.90±0.12, respectively. The apoptosis rates in control group, experimental-H group and 4-PBA group were (4.79±0.62)%, (23.01±2.03)% and (13.75±1.14)%, respectively. The expressions of CHOP protein in control group, experimental-H, si-NC and si-CHOP groups were 0.30±0.03, 0.92±0.08, 0.91±0.11 and 0.20±0.02, respectively; the apoptosis rates were (4.39±0.30)%, (22.11±1.82)%, (22.65±2.40)% and (15.32±1.19)%, respectively; mitochondrial cytochrome C (Cyto-C) protein levels were 0.78±0.07, 0.43±0.05, 0.42±0.05 and 0.65±0.06; cytoplasmic Cyto-C protein levels were 0.51±0.06, 0.91±0.10, 0.88±0.05 and 0.61±0.04; MMP levels were (100.00±2.79)%, (57.49±3.34)%, (54.09±4.32)% and (69.91±6.81)%, respectively. The above indexes in the experimental-L, -M, -H groups were compared with the control group, the above indexes in the 4-PBA group were compared with the experimental-H group, and the above indexes in the si-CHOP group were compared with the si-NC group, the differences were statistically significant (all P<0.01).

Aloperin can inhibit the proliferation of 253J cells by up-regulating the endoplasmic reticulum stress-dependent mitochondrial apoptosis pathway mediated by CHOP.

To study the effect of tazemetostat on the stemness of diffuse large B-cell lymphoma and the related mechanism of action.

OCI-LY3 cells were divided into blank group, tazemetostat group and microRNA-378a-3p (miR-378a-3p) mimics group. Blank group cell conventional culture; tazemetostat group was treated with 5 μmol·L^-1 tazemetostat; miR-378a-3p mimics group was transfected with miR-378a-3p mimics. The relative expression level of miR-378a-3p was detected by fluorescence in situ hybridization. mRNA expression levels of dryness related factors were detected by quantitative real time polymerase chain reaction; the expression of signal pathway-related proteins was detected by Western blot.

The relative expression levels of miR-378a-3p in blank group and tazemetostat group were 1.00±0.14 and 0.52±0.08, respectively, the difference was statistically significant (P<0.001). The relative expression of octamer binding transcription factor 4 mRNA in blank group, tazemetostat group and miR-378a-3p mimics group were 1.00±0.16, 0.21±0.06 and 0.49±0.08, respectively; the relative expression of sex determining region Y box protein 2 mRNA were 1.00±0.09, 0.39±0.05 and 0.85±0.11, respectively; the relative expression of Nanog homeobox mRNA were 1.00±0.13, 0.17±0.03 and 0.65±0.10, respectively; the relative expressions of Kruppel like factor 4 mRNA were 1.00±0.10, 0.28±0.05 and 0.86±0.14, respectively; the relative expressions of Yes associated protein were 1.00±0.19, 3.46±0.52 and 2.14±0.36, respectively; the relative expression of transcriptional coactivator with PDZ-binding motif protein were 1.00±0.14, 1.90±0.35 and 1.51±0.33, respectively. The above indexes of tazemetostat group were compared with those of blank group, and the above indexes of miR-378a-3p mimics group were compared with those of tazemetostat group, the differences were statistically significant (P<0.001, P<0.05).

Tazemetostat can inhibit the stemness of OCI-LY3 cells by down-regulating the level of miR-378a-3p, which may be achieved through the Yes associated protein/transcriptional coactivator with PDZ-binding motif signaling pathway.

To investigate the cardioprotective mechanism of Ilexin A in ameliorating hyperlipidemia through the regulation of microRNA-133a-3p (miR-133a-3p) and uncoupling protein 2 (UCP2).

Rats were randomly divided into control group (gavage with an equal volume of distilled water as the experimental group), model group (gavage with an equal volume of distilled water as the experimental group), experimental group (gavage with 40 mg·kg^-1 Ilexin A), miR-133a-3p inhibitor group (gavage with 40 mg·kg^-1 Ilexin A + tail vein injection of 1.95×10¹² vg·mL^-1 adenovirus containing miR-133a-3p inhibitor), and OE-UCP2 group (gavage with 40 mg·kg^-1 Ilexin A + tail vein injection of 1.95×10¹² vg·mL^-1 adenovirus containing both miR-133a-3p inhibitor and OE-UCP2). Blood lipid levels, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), were measured by enzyme-linked immunosorbent assay. Cardiac function parameters, such as the mitral inflow peak early diastolic velocity to late diastolic velocities (E/A) and left ventricular ejection fraction (LVEF), were assessed via echocardiography. The relative expression levels of mRNA were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR), while protein levels were detected by Western blot.

In the model and experimental groups, LDL-C levels were (0.92±0.12) and (0.76±0.09) mmol·L^-1; HDL-C levels were (0.82±0.10) and (1.14±0.13) mmol·L^-1; E/A ratios were 0.89±0.11 and 1.17±0.14; LVEF values were (41.31±5.07)% and (59.92±7.86)%; the relative expression levels of miR-133a-3p were 0.33±0.06 and 1.22±0.18; uncoupling protein 2 (UCP2) mRNA levels were 0.57±0.08 and 0.79±0.09; cleaved caspase-3 protein levels were 1.00±0.15 and 0.71±0.09; B-cell lymphoma-2 (Bcl-2) protein levels were 1.00±0.17 and 1.94±0.27, respectively. The differences between the model and experimental groups for these parameters were statistically significant (all P<0.05).

Ilexin A ameliorates hyperlipidemia by regulating miR-133a-3p and UCP2. Its mechanism may involve downregulating Bcl-2 and activating cleaved caspase-3 to induce apoptosis, thereby exerting cardioprotective effects and improving cardiac function.

To explore the effect and mechanism of piperlongumine on hepatic steatosis induced by sleep deprivation.

Mice were randomly divided into control group (normal feeding), model group (sleep deprivation treatment), low-, middle- and high dose groups (2.5, 5.0 and 10.0 mg·kg^-1 piperlongumine was given on the basis of sleep deprivation), and the mice were given continuous gavage for 14 days. Liver index was detected after 14 days of continuous gavage. Western blot assay was used to detect protein expression in hepatic tissue, lipid levels in hepatic tissue were detected by kit, and reactive oxygen species (ROS) levels in hepatic tissue were detected by dihydroethidium (DHE).

The liver index of control group, model group, and high-dose group were (2.99±0.40)%, (4.32±0.17)% and (3.30±0.37)%, respectively; triglyceride (TG) levels were (0.16±0.011), (0.29±0.02) and (0.17±0.02) mmol·mgprot^-1, respectively; fatty acid synthase (FAS) protein levels were 0.31±0.03, 0.69±0.08 and 0.35±0.03, respectively; hypoxia-inducing factor-1 α (HIF-1α) protein levels were 0.38±0.04, 0.94±0.08 and 0.44±0.04, respectively; the protein levels of adaptor p66Shc (p66Shc) were 0.21±0.03, 0.82±0.07 and 0.37±0.04, respectively; ROS levels were 1.00±0.09, 4.72±0.44 and 1.30±0.07, respectively. The above indexes in the model group were significantly different from those in the control group, and the above indexes in the high-dose groups were significantly different from those in the model group (all P<0.05).

Piperlongumine can improve liver steatosis induced by sleep deprivation in mice, which may be related to the regulation of HIF-1α/p66Shc signaling pathway.

To study the effect of hydroxylsafflower yellow A (HSYA) on epiphyseal injury of tibial in rats through neurotrophic factor-3 (NT-3).

Fifty male SD rats were randomly divided into control group, model group, HSYA group, NC group and sh-NT-3 group, with 10 rats in each group. Except the control group, the injury model of tibial epiphyseal was established in the other 4 groups by high speed dental abrasive drill. The HSYA group was given 10 mg·kg^-1 HSYA by intragastric administration once a day for 6 weeks. NC group and sh-NT-3 group were respectively injected with 1 mg·kg^-1 sh-NC and sh-NT-3 through the tail vein, once every two days for 6 weeks. The control group and model group were given the same amount of normal saline intragastric and caudal intravenous injection. Quantitative real-time polymerase chain reaction was used to detect the expression level of NT-3 mRNA. The expression levels of bone repair markers and Notch receptor 1 (Notch1) signaling pathway related proteins were detected by Western blot.

The mRNA levels of NT-3 in control group, model group and HSYA group were 1.00±0.17, 3.31±0.59 and 5.16±0.84, respectively. The relative expression of runt related transcription factor 2 protein in control group, model group, HSYA group, NC group and sh-NT-3 group were 1.00±0.17, 3.67±0.63, 7.36±1.35, 7.31±1.42, 5.74±1.32, respectively; the relative expressions of osteoblast-specific transcription factor protein were 1.00±0.18, 5.76±1.01, 8.49±1.42, 8.56±1.54, 6.48±1.16, respectively; the relative expressions of Notch1 protein were 1.00±0.18, 1.44±0.23, 1.79±0.34, 1.83±0.35, 1.52±0.27, respectively. The above indexes in the model group were compared with the control group, the HSYA group was compared with the model group, and the sh-NT-3 group was compared with the NC group, and the above indexes were statistically significant (all P<0.05).

HSYA improves tibial epiphyseal injury in rats by promoting NT-3 expression and activating Notch1 signaling pathway.

To study the effect and mechanism of galangin in improving depression-like behavior in vascular dementia (VD) mice through microRNA-134 (miRNA-134).

Seventy C57BL/6J mice were randomly divided into sham group (0.9% NaCl), model group (0.9% NaCl), low-dose group (25 mg·kg^-1 galangin), medium-dose group (50 mg·kg^-1 galangin), high-dose group (100 mg·kg^-1 galangin), and mimic NC group (100 mg·kg^-1 galangin and mimic NC 15 nmol), miRNA-134 mimic group (100 mg·kg^-1 galangin and miRNA-134 mimic 15 nmol). The degree of depression was detected by tail suspension test and forced swimming test; the level of corticosterone was detected by enzyme-linked immunosorbent assay; the level of miRNA-134 was detected by quantitative real time polymerase chain reaction; the apoptosis rate of brain tissue cells was detected by TdT-mediated dUTP nick-end labeling; and the level of synaptic plasticity related protein was detected by Western blot.

The suspension time of the sham group, the model group and the high-dose group were (105.32±15.22), (185.32±24.62) and (112.65±15.08) s, respectively; the swimming time were (86.52±13.25), (152.32±22.22) and (96.22±16.35) s respectively; the levels of corticosterone were (32.65±5.02), (86.62±14.32) and (48.52±5.55) ng·L^-1, respectively; the levels of miRNA-134 were 1.00±0.12, 2.32±0.35 and 1.21±0.18, respectively. The apoptosis rates of the sham group, model group, high group, mimic NC group and miRNA-134 mimic group were (5.32±0.62)%, (62.33±8.65)%, (14.32±1.78)%, (15.85±2.22)% and (43.21±7.05)%, respectively; synaptophysin protein levels were 1.00±0.18, 0.32±0.05, 0.88±0.12, 0.82±0.11 and 0.30±0.05, respectively; the postsynaptic density protein-95 protein levels were 1.00±0.14, 0.61±0.07, 0.72±0.09, 0.70±0.08 and 0.45±0.06, respectively. The above indexes in the model group were compared with those in the sham group, those in the high-dose group were compared with those in the model group, and those in the miRNA-134 mimic group were compared with those in the mimic NC group, and the differences were statistically significant (all P<0.05).

Galangin may improve the depression-like behavior of VD mice by inhibiting the expression of miRNA-134, improving synaptic plasticity and inhibiting cell apoptosis.

To study the pharmacokinetic profile of oseltamivir phosphate dry syrup in Chinese healthy subjects and to evaluate the bioequivalence and safety of the test formulation (T) and the reference formulation (R) under fasting and fed conditions.

In a randomized, open, two-agent, two-sequence, two-cycle, double-crossover trial design, 36 healthy subjects were enrolled in the fasting and fed groups, respectively, who received a single oral dose of 2.5 g of oseltamivir phosphate dry syrup of either the T or R. The blood concentrations of oseltamivir were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the pharmacokinetic parameters were calculated by using the WinNonlin (8.2) software and evaluated for bioequivalence and safety.

Under fasting conditions, the C_max of oseltamivir of the T and R were (64.40±17.50) and (64.10±20.90) ng·mL^-1, AUC_0-t were (142.76±43.64) and (151.60±35.10) h·ng·mL^-1, AUC_0-∞ were (147.67±37.60) and (153.05±35.30) h·ng·mL^-1, respectively. Under fed conditions, the C_max of oseltamivir of the T and R were (47.70±18.30) and (46.90±17.20) ng·mL^-1, AUC_0-t were (170.52±26.28) and (168.70±24.51) h·ng·mL^-1, AUC_0-∞ were (173.08±26.50) and (171.30±24.59) h·ng·mL^-1, respectively. The 90% confidence intervals for the geometric mean ratios of C_max, AUC_0-t and AUC_0-∞ for the T and R fell in the range of 80.00% to 125.00% for both the fasting and fed groups. Adverse drug reaction rates were 27.78% and 44.44% in the fasting and fed groups, respectively.

Two kinds of oseltamivir phosphate dry syrups were bioequivalent and had favorable safety profiles in Chinese healthy subjects in both fasted and fed states.

To establish a high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method for the determination of nicorandil concentrations in human plasma and for pharmacokinetic studies in healthy subjects.

Human plasma samples were pretreated with acetonitrile extraction. Chromatographic cdumn: Acquity HPLC BEH C₁₈ (1.7 μm, 2.1 mm×50.0 mm), mobile phase: methanol (0.1% formic acid)-5 mmoL· L^-1 ammonium acetate (with 0.1% formic acid). Flow rate: 0.2 mL·min^-1, column temperature: 40 ℃, injection volume: 5 μL. Gradient elution, electrospray ion source, multiple reaction monitoring, positive ion scanning, nicorandil-d4 isotope as internal standard. The specificity of the method, the standard curve and the lower limit of quantification, the carryover effect and dilution reliability, the precision and recovery, the matrix effect, and the stability of the method were investigated.

The specificity of the established method was good, nicorandil had a good linear relationship between 0.2-200.0 ng·mL^-1, the standard curve was y=1.08×10^-1x+2.66×10^-2 (r=0.999 7), the lower limit of quantification was 0.2 ng·mL^-1, there was no residual effect, the dilution results were reliable, and the intra-day and inter-day precision of quality control samples were 0.64%-8.70% and 0.91%-8.70%, respectively. The intra-day and inter-day accuracy were 100.00%-115.00% and 98.00%-115.00%, respectively. The extraction recoveries of nicorandil at low, medium and high quality control concentrations were 92.78%-95.35%, with no obvious matrix effect and good stability.

This method is highly specific, accurate, stable, reproducible, and simple to operate, and can be used to determine the concentration of drug in plasma of nicorandil.

To establish an ultra-high performance liquid chromatography tandem high resolution mass spectrometry (UHPLC-HRMS) method for the determination of serum demthylzeylasteral concentration in diabetic nephropathy patients, which treated by tripterygium wilfordii polyglycosides tablets (TGTs), and to apply this method in the exploratory study of clinical pharmacodynamic marker.

Serum samples and ¹⁸O-demethylzeylasteral which was used as the internal standard were processed by solid phase extraction method and took the supernatant for the determination. Chromatographic separation of the analytes was accomplished using a BEH C₁₈ column (2.1 mm×50.0 mm, 1.7 μm) under gradient elution, where the mobile phase consisted of a mixture of 0.1% formic acid aqueous solution and acetonitrile, as well as 0.1% formic acid aqueous solution. The flow rate was set at 0.3 mL·min^-1 and the column temperature at 30 ℃. The mass spectrometer was equipped with an electrospray ionization source with positive multiple reaction monitoring mode. The specificity, standard curve and lower limit of quantification, precision and recovery rate, matrix effect and stability were investigated. This method was applied to determine the serum concentration of demethylzeylasteral from 15 patients with oral TGTs. Receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were utilized to explore the correlation between serum concentration of demethylzeylasteral and efficacy in treating diabetic nephropathy.

The calibration curve of demethylezylasteral was linear over the range of 1-200 ng·mL^-1, and the lower limit of quantification was 1 ng·mL^-1. The precision and accuracy relative standard deviation of intra-day and inter-day was less than 10% and 15%, respectively. The average absolute recovery was more than 89%, no matrix effect has been affected and all stability tests met the acceptance criteria. The AUC of the efficacy of TGTs predicted by serum demethylzeylasteral quantitation was 0.66 (95% confidence interval was 0.53-0.78), the cut-off value was 61.73 ng·mL^-1, the sensitivity was 83.3% and the specificity was 46.7% (P<0.05).

The UHPLC-HRMS method established in this study has the advantages of simple operation, high sensitivity, accurate and reliable results, which can be suitable for determining serum concentration of demethylzsylasteral and studying clinical drug efficacy markers of TGTs.

Acute lung injury (ALI)/acute respiratory distress syndrome is a life-threatening acute diffuse inflammatory lung injury characterised by increased pulmonary vascular permeability, inflammatory cell infiltration, pulmonary oedema, diffuse alveolar damage and reduced respiratory output. Its pathogenesis is complex, and oxidative stress is a key mechanism leading to ALI exacerbated by alveolar epithelial cell dysfunction. The Kelch-like ECH associated protein 1 /nuclear factor -E2-related factor 2 (Keap1/Nrf2) signalling pathway is an important signalling pathway of traditional Chinese medicine in the treatment of ALI by regulating oxidative stress. This paper analyses and summarizes the relevant Chinese medicine formulas and active ingredients for the treatment of ALI, and finds that a large number of antioxidant active ingredients can regulate oxidative stress through the Keap1/Nrf2 signaling pathway and play a role in improving ALI, which also provides a basis for the prevention and treatment of ALI disease and further drug development.