To observe the effects of empagliflozin tablets-assisted therapy on end-diastolic volume and major cardiovascular adverse events in patients with mild reduced EF heart failure (HFmrEF).

Patients with HFmrEF were divided into control group and treatment group by queue method. The control group received conventional treatment. The treatment group was given empagliflozin tablets in addition to control group, 10 mg each time (starting dose and target dose were both 10 mg), orally on an empty stomach in the morning, once a day. Both groups of patients were treated for 6 months. The clinical efficacy, end-diastolic volume including left ventricular end-diastolic area (LVEDA) and left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), myocardial markers including cardiac troponin I (cTnI) and N-terminal B-type natriuretic peptide (NT-proBNP), major adverse cardiovascular events and safety were compared between the two groups.

Both groups had no cases dropped out, with 60 cases in control group and 60 cases in treatment group. After treatment, the total effective rates of treatment group and control group were 95.00% (57 cases/60 cases) and 81.67% (49 cases/60 cases), respectively, with statistically significant difference (P<0.05). After treatment, the LVEF of treatment group and control group were (56.20±5.12)% and (50.25±4.26)%, LVEDV were (142.58±15.58) and (165.28±18.59) mL, LVEDA were (36.28±3.41) and (39.62±3.56) cm², serum NT-proBNP levels were (869.48±135.29) and (1 459.87±158.69) pg·mL^-1, cTnI levels were (7.02±1.65) and (9.28±1.74) ng·L^-1, respectively, and the incidence of major cardiovascular adverse events in treatment group and control group were 5.00% and 16.67%. The above indexes in treatment group had statistical significant differences compared with control group (all P<0.05). The adverse drug reactions of treatment group mainly include headache, hyperkalemia, hypotension and gastrointestinal reactions, while the adverse drug reactions of control group mainly include hyperkalemia, headache and hypotension. During the treatment, the incidence of adverse drug reactions in treatment group and control group were 8.33% and 5.00%, respectively (P>0.05).

Adjuvant treatment with empagliflozin tablets can improve the overall therapeutic effect of HFmrEF, improve the end diastolic volume index and LVEF of patients, regulate myocardial marker indicators, reduce the incidence of major cardiovascular adverse events, and has good safety.

To explore the clinical efficacy and safety of beraprost sodium tablets combined with alprostadil injection in patients with stage Ⅲ diabetic nephropathy.

According to queuing method, inpatients with stage Ⅲ diabetic nephropathy treated in the hospital were divided into treatment group and control group. Treatment group was treated with beraprost sodium tablets + alprostadil injection (the first 2 weeks: intravenous drip of alprostadil injection 10 μg qd. the last 2 weeks: oral beraprost sodium tables 40 μg tid), while control group was treated with alprostadil injection (the same administration method as treatment group for 4 weeks). The clinical efficacy, β2 microglobulin (β2-MG), cystatin C (Cys-C), blood urea nitrogen (BUN), serum creatinine (SCr), urinary albumin to creatinine ratio (UACR), transforming growth factor β1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), hemoglobin Alc (HbAlc), fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG), homeostasis model assessment for insulin resistance (HOMA-IR), hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were compared between the two groups, and the safety was evaluated.

Among the 103 patients, there were 52 cases in treatment group and 51 cases in control group. The efficiency rate in treatment group was higher than that in control group [92.31% (48 cases/52 cases) vs. 78.43% (40 cases/51 cases), P<0.05]. After treatment, levels of serum β2-MG in treatment group and control group were (0.25±0.06) and (0.31±0.07) mg·L^-1, BUN levels were (5.70±0.91) and (6.89±1.01) mmol·L^-1, SCr levels were (85.46±8.89) and (93.88±9.77) μmol·L^-1, Cys-C levels were (1.38±0.26) and (1.64±0.30) mg·L^-1, UACR levels were (140.24±31.04) and (176.40±36.19) mg·g^-1, respectively; levels of serum TIMP-1 were (88.34±12.36) and (97.62±15.44) ng·mL^-1, TGF-β1 levels were (112.49±17.24) and (138.50±19.84) ng·mL^-1, MMP-9 levels were (130.69±21.30) and (114.79±19.77) μg·L^-1, respectively; levels of serum IL-6 were (141.49±28.85) and (173.49±32.36) pg·mL^-1, hs-CRP levels were (7.64±1.16) and (9.29±1.54) mg·L^-1, TNF-α levels were (23.65±4.34) and (29.12±3.86) pg·mL^-1, and differences in the above indexes between treatment group and control group were all statistically significant (all P<0.05). During treatment, there was 1 case with diarrhea, 1 case with rash and 1 case with nausea and vomiting in treatment group, while there was 1 case with rash and 1 case with diarrhea in control group. There was no statistically significant difference in incidence of adverse drug reactions between treatment group and control group (5.77% vs. 3.92%, P>0.05).

Alprostadil injection combined with beraprost sodium tablets can effectively improve renal function, regulate metabolism of extracellular matrixes in renal tissues, relieve inflammatory response and improve clinical curative effect in patients with stage Ⅲ diabetic nephropathy.

To explore the antidepressant effect and its mechanism of effective components of Lilium brownii based on brain-derived neurotrophic factor/protein kinase B/mammalian target of rapamycin (BDNF/AKT/mTOR) pathway.

In cellular experiments, the experiments were divided into control group (cell culture solution), model group (corticosterone 400 μmol·L^-1), lily saponin low dose group (corticosterone 400 μmol·L^-1+0.2 mg·L^-1 liliy saponin), lily saponin high dose group (corticosterone 400 μmol·L^-1+0.6 mg·L^-1 liliy saponin), lily polysaccharide low dose group (corticosterone 400 μmol·L^-1+0.2 mg·L^-1 liliy polysaccharide), and lily polysaccharide high dose group (corticosterone 400 μmol·L^-1+0.6 mg·L^-1 liliy polysaccharide). Except for the blank group, the remaining groups were modeled with corticosterone to establish human neuroblastoma cells (SH-SY5Y) injury, and cell survival was detected. In the animal experiments, 48 male ICR mice were randomly divided into 6 groups: model group (drinking water with the same amount), low dose of lily saponin (50 mg·kg^-1), high dose of lily saponin (100 mg·kg^-1), low dose of lily polysaccharide (50 mg·kg^-1), high dose of lily polysaccharide (100 mg·kg^-1) and positive drug control group (fluoxetine,10 mg·kg^-1). Each group was given acute stress modeling in mice, and changes in behavioral indexes were observed. Serum corticosterone levels were measured by enzyme-linked immunosorbent assay. The relative expression levels of proteins such as postsynaptic densifier 95 (PSD95) and synapsin in the prefrontal cortex of mice were detected by protein immunoblot analysis.

In the cellular experiments, the cell survival rates of each subgroup were (71.46±1.92)%, (95.97±1.11)%, (105.51±1.80)%, (107.48±0.27)% and (107.66±3.61)%, respectively. The differences between the administered groups and the model group were all statistically significant (all P<0.01). In the animal experiments, the cumulative immobilization time of mice with suspended tails in model group, low and high dose of lily saponin groups, low and high dose of lily polysaccharide group and positive drug group was (122.75±4.77), (90.75±2.09), (66.13±3.23), (79.75±2.84), (54.38±4.40), and (42.00±6.34) s, respectively; the levels of corticosterone in the serum of mice were (236.94±6.17), (213.88±3.95), (165.52±2.19), (203.40±3.27), (170.18±2.18) and (104.96±3.87) ng·mL^-1, respectively; the relative expression levels of brain-derived neurotrophic factor (BDNF) were 0.26±0.03, 0.74±0.25, 0.86±0.03, 0.97±0.11, 0.92±0.13 and 1.05±0.23, respectively; the relative expression levels of phosphorylated protein kinase B/protein kinase B (p-AKT/AKT) were 0.26±0.03, 0.60±0.19, 0.75±0.09, 0.82±0.05, 0.94±0.23 and 0.58±0.07, respectively; the relative expression levels of phosphorylated mammalian target of rapamycin/mammalian target of rapamycin protein (p-mTOR/mTOR) were 0.46±0.04, 0.52±0.19, 0.60±0.18, 1.01±0.01, 0.98±0.06 and 0.93±0.10, respectively; the relative expression levels of postsynaptic density protein-95 (PSD95) were 0.36±0.05, 0.50±0.08, 0.60±0.09, 0.73±0.09, 0.84±0.18 and 1.00±0.12, respectively; the relative expression levels of synapsin protein were 0.13±0.04, 1.03±0.02, 1.16±0.06, 1.02±0.00, 1.00±0.04 and 0.65±0.15, respectively. Except the p-mTOR/mTOR and PSD95 in high dose of lily saponin, the differences of the above indexes between the model group and the high dose groups were all statistically significant (P<0.05, P<0.01).

Lily saponins and polysaccharides may improve synaptic plasticity in prefrontal cortex by modulating the BDNF/AKT/mTOR signaling pathway, which improves depressive-like behavior and suppresses serum corticosterone levels in behavioral despair mice. Among them, lily polysaccharides were slightly better than lily saponins in improving synaptic plasticity.

To establish a rat model of renal fibrosis induced by unilateral ureteral obstruction (UUO), and investigate the mechanism of the Yishen Qufeng Formula (YQF) improves renal fibrosis through regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis to mediate ferroptosis.

Eight-week-old SD rats were randomly divided into the sham-operation group, model group, positive control group (dapagliflozin at 20 mg·kg^-1·d^-1), and experimental -L,-M,-H groups (Yishen Qufeng Formula at 15.21, 22.82 and 30.42 g·kg^-1·d^-1). Except for the sham operation group, rats in the other groups were subjected to left ureteral ligation to establish a renal interstitial fibrosis (RIF) model. After successful modeling, the positive control group and the -L, -M, and -H dose experimental groups were given the corresponding drugs by gavage, while the sham operation group and model group were given an equal volume of 0.9% NaCl by gavage. All rats in the 6 groups were administered once a day for 14 consecutive days. Serum creatinine, urea nitrogen and urine protein levels were detected using a fully automatic integrated biochemical analyzer. The content of transforming growth factor-β1 (TGF-β1) was measured by enzyme-linked immunosorbent assay (ELISA). The changes in the relative expression levels of fibrosis-related, oxidative stress-related and ferroptosis-related proteins in renal tissues were determined by Western blotting.

The levels of serum creatinine in the experimental -M, -H groups, sham operation group, model group and positive control group were (50.24±7.81), (49.15±8.87), (41.96±5.25), (59.44±11.93) and (52.14±8.38)μmol·L^-1, respectively; the levels of urea nitrogen were (4.58±0.56), (4.45±0.55), (4.32±0.60), (6.00±1.03) and (6.55±1.02)mmol·L^-1, respectively; the levels of urine protein were (640.59±205.70), (538.74±237.98), (526.51±192.62), (982.91±349.13) and (964.26±456.84)mg·d^-1, respectively; the relative protein expression levels of glutathione peroxidase 4 (GPX4) were 1.62±0.15, 3.01±0.41, 2.25±0.27, 1.01±0.51 and 2.15±0.63, respectively; the relative protein expression levels of cystine/glutamate antiporter (xCT) were 0.62±0.10, 1.02±0.06, 1.65±0.13, 0.52±0.20 and 1.18±0.13, respectively; the relative protein expression levels of Nrf2 were 0.66±0.12, 1.04±0.16, 1.20±0.10, 0.54±0.03 and 1.19±0.14, respectively; the relative protein expression levels of HO-1 were 1.13±0.15, 1.21±0.18, 2.21±0.17, 0.64±0.44 and 1.57±0.26, respectively; the relative protein expression levels of α-smooth muscle actin (α-SMA) were 1.63±0.47, 1.13±0.57, 0.49±0.91, 2.88±0.97 and 1.05±0.60, respectively. There were statistically significant differences in the above indicators between the high-dose experimental group and the model group (all P<0.05).

Yishen Qufeng Formula may inhibit ferroptosis by activating the Nrf2/HO-1 signaling pathway, thereby effectively alleviating renal interstitial fibrosis in UUO rats. This provides important theoretical evidence for the mechanism by which the Yishen Qufeng Formula improves renal fibrosis through regulation of ferroptosis.

To analyze the anticoagulant treatment of patients with low molecular weight heparin-induced severe type II thrombocytopenia complicated by multi-site embolism, and to provide reference for rational use of anticoagulant drugs in clinic.

Clinical pharmacists participated in the diagnosis and treatment of a patient with heparin-induced thrombocytopenia(HIT) with multiple thrombus. According to the patient’s pathophysiology, auxiliary examination and other conditions, combined with literature review and individualized medication monitoring, they assisted in formulating and optimizing the anticoagulant treatment plan, improving the quality of pharmaceutical care, and promoting clinical rational drug use.

The clinical pharmacist assisted in identifying the cause of thrombocytopenia, with a 4T’s HIT score of 7 (indicating high probability of HIT) and positive HIT antibody(HIT-Ab) (6.2 U·mL^-1). Following argatroban anticoagulation therapy, the patient’s blood platelet count (PLT) improved from 11 to 87 ×10 ·L^-1, while D-dimer levels peaked at 60.08 mg·L^-1 FEU before declining to 30.60 mg·L^-1 FEU. Activated partial thromboplastin time (APTT) remained stable at approximately 50 seconds. No new thrombotic or hemorrhagic events occurred, and the clinical outcome was favorable.

Although low molecular weight heparin-induced thrombocytopenia is rare, it still needs clinical attention. Clinical pharmacists can assist physicians in formulating individualized treatment plans for patients from the perspective of pharmaceutical professionals to ensure the rationality of clinical drug use.

To explore the effect and potential mechanism of hyperuricemia (HUA) on acetaminophen (APAP)-induced liver injury.

Male mice were randomly divided into four groups: group A (control), group B [establishment of a hyperuricemia (HUA) model], group C (administered by oral gavage at a dose of 300 mg·kg^-1 APAP), and group D (establishment of a HUA model combined with administered by oral gavage at a dose of 300 mg·kg^-1 APAP). The HUA model was established by intraperitoneal injection of potassium oxonate (350 mg·kg^-1) and gavage of xanthine (450 mg·kg^-1) for 14 consecutive days. On day 13, mice in group C and group D received APAP via gavage. All mice were sacrificed 24 h later. Serum levels of uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined by biochemical analyzer. Liver histopathology was evaluated by hematoxylin-eosin (H&E) staining. Levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in liver tissues were measured using commercial kits. Immunofluorescence was used to detect the relative expression of nuclear factor erythroid 2-related factor 2 (Nrf2).

The serum uric acid levels in the group A, group B, group C and group D were (186.20±15.61), (521.50±56.81), (325.20±31.74) and (682.00±49.51) μmol·L^-1, respectively; the liver coefficients were (4.51±0.14)%, (4.77±0.23)%, (4.98±0.21)%, and (5.51±0.30)%, respectively; the serum ALT levels were (55.80±15.86), (78.09±10.92), (27 688.81±7 166.01), and (34 571.89±7 793.74) U·L^-1, respectively; the AST levels were (159.90±29.72), (143.70±26.46), (10 880.00±4 291.01), and (19 824.84±7 874.64) U·L^-1, respectively; the hepatic MDA contents were (5.42±0.38), (7.77±0.32), (6.07±0.31), and (9.08±0.36) mol·g^-1·prot^-1, respectively; the ROS contents were (28.09±3.52), (39.67±2.70), (32.22±4.71), and (45.67±2.71) μg·g^-1·prot^-1, respectively; the GSH levels were (2.47±0.27), (1.72±0.16), (2.24±0.16), and (1.37±0.11) μg·g^-1·prot^-1, respectively; the IL-1β contents were (22.16±0.88), (31.74±1.82), (25.35±1.07), and (38.82±1.68) μg·g^-1·prot^-1, respectively; the TNF-α contents were (114.90±10.60), (180.20±3.72), (142.20±4.69), and (228.10±17.33) μg·g^-1·prot^-1, respectively; the relative protein expression of Nrf2 were 218.30±5.16, 63.60±29.02, 100.80±23.60, and 9.31±8.83, respectively. The indices in groups B and C were significantly different from those in group A, and the indices in group D were significantly different from those in group C, with all differences showing statistical significance (P<0.05).

In the hyperuricemia (HUA) mouse model, the liver damage induced by acetaminophen (APAP) is aggravated, and this effect may be related to the downregulation of NRF2 expression.

Evaluate whether the test formulation and reference formulation of bisoprolol amlodipine tablets are bioequivalent after a single oral administration in healthy subjects under fasting and postprandial conditions.

A single-dose, randomized, open-label, two-period, self-crossover trial design was adopted. Fasting and postprandial tests were randomly divided into 2 administration sequence groups according to 1∶1 ratio, the subjects were administered orally one tablet of either the test or reference formulation of the bisoprolol-amlodipine tablet, containing 5 mg bisoprolol fumarate and 5 mg amlodipine besylate (equivalent to 5 mg amlodipine). Liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) was applied to determine the concentration of bisoprolol and amlodipine in plasma of healthy subjects after fasting or fed administration, while Phoenix WinNonlin 8.1 software were used for pharmacokinetics (PK) parameters calculation and bioequivalence analysis.

Healthy subjects took one tablet of test product (T) and the reference product (R), under fasting condition. The main pharmacokinetic parameters of bisoprolol were as follows: C_max were (26.94±5.93) and (27.85±6.06) ng·mL^-1, respectively; AUC_0-t were (325.81±59.30) and (345.77±87.04) ng·mL^-1·h^-1, respectively; AUC_0→∞ were (337.94±63.91) and (360.03±95.94) ng·mL^-1·h^-1, respectively; the main pharmacokinetic parameters of amlodipine were as follows: C_max were (3.56±0.89) and (3.63±0.93) ng·mL^-1, respectively; AUC_0-t were (165.78±47.60) and (170.76±48.63) ng·mL^-1·h^-1, respectively; AUC_0→∞ were (188.76±67.62) and (188.40±54.85) ng·mL^-1·h^-1, respectively; the 90% confidence intervals of C_max、AUC_0-t and AUC_0-∞ after logarithmic conversion of bisoprolol and amlodipine of the two products were all within 80.00%-125.00%. Healthy subjects took the test and reference product under fed condition. The main pharmacokinetic parameters of bisoprolol were as follows: C_max were (22.66±2.91) and (22.68±3.85) ng·mL^-1, respectively; AUC_0-t were (310.42±59.44) and (303.39±53.21) ng·mL^-1·h^-1, respectively; AUC_0→∞ were (320.68±67.30) and (313.31±60.15) ng·mL^-1·h^-1, respectively; the main pharmacokinetic parameters of amlodipine were as follows: C_max were (3.24±0.53) and (3.15±0.55) ng·mL^-1, respectively; AUC_0-t were (180.74±40.77) and (178.27±33.53) ng·mL^-1·h^-1, respectively; AUC_0→∞ were (199.02±50.12) and (197.77±39.64) ng·mL^-1·h^-1, respectively. The 90% confidence intervals of C_max、AUC_0-t and AUC_0-∞ after logarithmic conversion of bisoprolol and amlodipine of the two products were all within 80.00%-125.00%.

Healthy adult subjects demonstrate bioequivalence between the test formulation and reference formulation of bisoprolol amlodipine tablets following a single oral administration under both fasting and postprandial conditions.

To explore the effects of ropivacaine on the cyclic guanosine monophosphate synthase interferon gene stimulating factor (cGAS/STING) pathway in glial cells of septic encephalopathy (SAE) model mice, and its related mechanisms of action.

Mice were randomly divided into blank group, model group, experimental group and control group, with 15 mice in each group. Except for the blank group and control group, the other two groups were used to establish sepsis mouse models by intraperitoneal injection of lipopolysaccharide. The experimental group and control group were intraperitoneally injected with 0.3 mg·kg^-1·d^-1 ropivacaine, while the blank group and model group were intraperitoneally injected with an equal volume of 0.9% NaCl. The four groups of mice were administered once a day for 7 consecutive days. The Morris water maze was used to detect the cognitive function of the mouse brain, real-time fluorescent quantitative polymerase chain reaction was used to detect the mRNA levels of brain inflammatory factors, Western blot was used to detect the expression levels of brain cGAS and STING proteins, and immunofluorescence staining was used to detect the expression of apoptosis-related proteins.

The exploration time proportions of the blank group, model group, experimental group and control group were (0.48±0.10)%, (0.23±0.05)%, (0.37±0.04)% and (0.46±0.07)%, respectively; the platform crossing times were (4.67±0.48), (1.03±0.11), (2.50±0.65) and (4.99±0.52) times, respectively; the escape latency time was (11.92±0.98), (12.49±1.22), (11.17±1.43) and (12.21±1.52) min, respectively; the relative expression levels of interleukin-1β (IL-1β) mRNA were 1.00±0.10, 3.80±0.28, 1.87±0.13 and 1.06±0.29, respectively; the relative expression levels of IL-18 mRNA were 1.00±0.12, 1.61±0.27, 1.06±0.08 and 0.97±0.05, respectively; the relative expression levels of tumor necrosis factor (TNF)-α mRNA were 1.00±0.13, 2.02±0.18, 1.05±0.09 and 1.13±0.11, respectively; the relative expression levels of IL-6 mRNA were 1.00±0.08, 1.56±0.11, 1.05±0.09 and 0.93±0.06, respectively; the relative expression levels of cGAS protein were 1.00±0.08, 1.92±0.19, 1.42±0.11 and 1.03±0.10, respectively; the relative expression levels of STING protein were 1.00±0.12, 2.01±0.22, 1.18±0.09 and 1.08±0.16, respectively; the relative fluorescence intensities of cGAS protein were 1.00±0.18, 1.88±0.15, 1.57±0.09 and 1.03±0.11, respectively; the relative fluorescence intensities of STING were 1.00±0.16, 1.79±0.26, 1.14±0.06 and 1.20±0.29, respectively; the relative fluorescence intensities of caspase-3 protein were 1.00±0.12, 1.51±0.08, 1.23±0.10, and 1.11±0.15, respectively. The above indexes of the experimental group and the control group were statistically different from the model group (all P<0.05).

Ropivacaine can alleviate apoptosis of glial cells in the hippocampus of SAE mice by inhibiting the cGAS/STING pathway, and has a protective effect on the brain of SAE mice.