To establish an ultra performance liquid chromatography (UPLC) method for determining the concentration of pazopanib in human serum.

Carbamazepine was used as an internal standard (IS), and acetonitrile as a protein precipitant. Separation was performed on an Agilent InfinityLab Poroshell 120 EC-C₁₈ column (2.1 x 50 mm, 1.9 μm) with a mobile phase of 0.1% aqueous formic acid-acetonitrile solution in gradient elution mode. The flow rate was 0.25 mL·min^-1, detection wavelength was 268 nm, column temperature was 40 ℃, and injection volume was 25 μL. The specificity of the method, the standard curve and the lower limit of quantification, the accuracy and precision and the stability of the sample were investigated.

Under the established chromatographic conditions, the analyte and internal standard exhibited satisfactory separation without interference from endogenous substances. Pazopanib demonstrated good linearity within the concentration range of 0.5-100 μg·mL^-1. The standard curve was y=63.37×10^-2x-0.49×10^-2 (r²=0.999 9) and the lower limit of quantification can reach 0.25 μg·mL^-1. The relative standard deviations (RSD) for both intra-day. and inter-day precision were less than 12.02%, with extraction recovery rates exceeding 86.44%. Stability was good, with RSD below than 8.80%.

The established UPLC method is simple, selective, sensitive, accurate, and reliable for determining pazopanib in human serum.

To analyze the gene polymorphism of aspirin drug-related genes platelet membrane glycoprotein Ⅲa phospholipase A2 (GPⅢa PLA2), platelet endothelial aggregation receptor 1 (PEAR1), glutathione S-transferase P1 (GSTP1) and prostaglandin endoperoxide synthase 1 (PTGS1) in patients with ischemic stroke in Beijing.

Patients with ischemic stroke in the neurology department of our hospital were included as research subjects, and the polymorphism of drug-related gene loci was detected by fluorescence in situ hybridization sequencing.

The overall mutation rate of aspirin related genes was 75.42% (356 cases/472 cases). GPⅢa PLA 2 typing included 458 cases TT type, 11 cases TC type and 3 cases CC type, C allele frequency was 1.80% (17 cases/944 cases); PEAR1 typing included 187 cases GG type, 224 cases GA type and 61 cases AA type, A allele frequency was 36.65% (346 cases/944 cases); GSTP1 typing included 295 cases AA type, 160 cases GA type and 17 cases GG type, G allele frequency was 20.55% (194 cases/944 cases); typing of PTGS1 included 50 cases AA type, and the frequency of G allele was 0. GPⅢa PLA2 TT+PEAR1 GA+GSTP1 AA was the most common combination, accounting for 138 cases (29.24%). There was no statistically significant difference in gene polymorphisms of GPⅢa PLA2, PEAR1, GSTP1 between different genders and ages (all P>0.05). The genotype and allele distributions of GPⅢa PLA2, PEAR1, GSTP1 and PTGS1 in patients with ischemic stroke in Beijing were not statistically significantly different from those in Zaozhuang, Nanjing and Shanghai (all P>0.05), while the genotype and allele distributions of GPⅢa PLA2, PEAR1 and GSTP1 were statistically significantly different from those in Guangdong (all P<0.05).

PEAR1 and GSTP1 are the main mutations in aspirin drug-related genes in patients with ischemic stroke in Beijing. The mutation ratio of GPⅢa PLA2 and PTGS1 gene is low, and the gene polymorphism in Beijing is different from that in other regions.

To observe the clinical efficacy and safety of cinacalcet tablets combined with calcitriol pills in diabetic nephropathy (DN) patients undergoing hemodialysis.

DN patients receiving hemodialysis in our hospital were divided into treatment group and control group based on different medication regimens. The control group was treated with calcitriol pills, administered orally twice a week. The dosage was 0.25-1.5 μg for patients with intact parathyroid hormone (iPTH) 300-600 ng·L^-1, 0.5-2.0 μg for those with (iPTH) 600-1 000 ng·L^-1, and 2.0-4.0 μg for those with iPTH > 1 000 ng·L^-1. The treatment group received cinacalcet tablets in addition to the control group’s treatment. The initial dose of cinacalcet tablet was 25 mg per day, adjusted every 2-4 weeks, the dose remained unchanged for patients with serum calcium < 2.1 mmol·L^-1; increased to 50 mg per day for those with serum calcium>2.0 mmol·L^-1; and decreased to 75 mg per day for those with serum calcium<1.8 mmol·L^-1. Both groups were treated for 6 months. Clinical efficacy, calcium-phosphorus metabolism, renal function, bone metabolism, iPTH levels and parathyroid gland volume were compared between the two groups, and safety was evaluated.

A total of 94 patients were included in this study, with 47 cases in each of treatment and control groups. After treatment, the total effective rates were 95.74% (45 cases/47 cases) in treatment group and 80.85% (38 cases /47 cases) in control group, showing statistically significant difference (P<0.05). After treatment, the blood calcium levels in treatment and control groups were (2.78±0.21) and (2.49±0.23) mmol·L^-1, respectively; blood phosphorus levels were (1.11±0.13) and (1.39±0.17) mmol·L^-1, respectively; calcium-phosphorus product levels were 3.09±0.24 and 3.46±0.29, respectively; fibroblast growth factor 23 (FGF23) levels were (60.55±7.21) and (71.62±7.84) ng·L^-1, respectively; alkaline phosphatase levels were (91.06±28.43) and (110.35±32.19) U·L^-1, respectively; osteoprotegerin levels were (6 892.43±395.46) and (7 142.58±411.27) ng·L^-1, respectively; iPTH levels were (623.08±57.19) and (721.57±61.46) ng·L^-1, respectively; and parathyroid gland volumes were (0.81±0.19) and (1.11±0.18) cm³, respectively. All of these indicators in treatment group showed statistically significant differences compared to control group (all P<0.05). The main adverse drug reactions in treatment group included pruritus (2 cases), myalgia (3 cases), nausea and vomiting (1 case) and diarrhea (1 case). In the control group, adverse drug reactions were pruritus (1 case), myalgia (2 cases), nausea and vomiting (2 cases) and diarrhea (1 case). The total incidence of adverse drug reactions were 12.77% (6 cases/47 cases) in treatment group and 14.89% (7 cases/47 cases) in control group, with no statistically significant difference (P>0.05).

The combination of cinacalcet tablets and calcitriol pills effectively corrects disorders of calcium-phosphorus and bone metabolism, reduces iPTH levels, and decreases parathyroid gland volume in DN patients on hemodialysis, with a favorable safety profile.

To explore the intervention effect of jiedu dihuang decoction on the inflammatory microenvironment of colon cancer by regulating mitophagy and nucleotide - binding oligomerization domain (NOD) like receptor hot protein domain-related protein 3 (NLRP3) inflammasome.

The animal model was successfully replicated by intraperitoneal injection of azoxymethane (AOM) combined with feeding dextran sodium sulfate (DSS). The animals were randomly divided into A: control group, B: model group, C, D, E: Jiedu Dihuang Decoction low, medium and high dose group, F: positive drug group. Ninety male C57BL/6 mice were randomly divided into 6 groups of 15 mice each, and all groups were treated continuously for 10 weeks. The pathological changes of rectal tissue were evaluated by hematoxylin-eosin (HE) staining. Immunofluorescence staining was used to observe the expression site and intensity of PTEN-induced kinase 1 (PINK1), Parkinson’s disease protein (Parkin) and B-cell lymphoma-2-interacting myosin-like coiled-coil protein 1 (Beclin1) in colon tissue. The expression of NLRP3, apoptosis-associated speck-like protein (ASC) and Caspase-1 mRNA in rectum was detected by polymerase chain reaction (PCR). The protein expression levels of PINK1, Parkin, Beclin1, NLRP3, ASC and Caspase-1 were detected by Western blotting (WB). The ratio of helper T cell 1 (Th1) to helper T cell 2 (Th2) was detected by flow cytometry. The levels of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay (Elisa).

The mRNA expression levels of NLRP3, ASC and Caspase-1 in the model group were 2.06±0.22, 3.03±0.16 and 3.28±0.22, respectively, while those in the control group were 1.01±0.17, 1.01±0.19 and 1.00±0.11, respectively, with statistically significant differences between the two groups (all P<0.01). The mean fluorescence intensities of PINK1, Parkin and Beclin1 in the model group were 76.39±4.89, 83.12±5.01 and 87.43±3.77, respectively, compared with 122.99±6.93, 138.38±3.84 and 143.22±9.42 in the control group, and the differences were statistically significant (all P<0.01). As for the proportion of T helper cells in peritoneal fluid, the model group showed a significantly lower Th1 proportion (0.74±0.09)% and a significantly higher Th2 proportion (2.05±0.26)% compared with the control group [(4.78±0.62)% and (0.26±0.07)%, respectively, all P<0.01]. In terms of peripheral blood cytokine levels, the concentrations of IL-4, IL-6, IL-10 and TNF-α in the model group were (48.98±3.78) pg·mL^-1, (44.42±2.55) pg·mL^-1, (37.67±5.34) pg·mL^-1 and (79.11±6.32) pg·mL^-1, respectively, which were significantly higher than those in the control group [(26.44±5.64) pg·mL^-1, (24.21±2.25) pg·mL^-1, (19.06±3.76) pg·mL^-1 and (35.78±13.17) pg·mL^-1, respectively]. Conversely, the levels of IL-12 and IFN-γ in the model group were (28.28±2.33) ng·mL^-1 and (238.67±35.78) pg·mL^-1, respectively, which were significantly lower than those in the control group [(55.39±3.47) ng·mL^-1 and (517.72±52.15) pg·mL^-1, respectively], with all differences reaching statistical significance (all P<0.01). The mRNA expression levels of NLRP3 in the low, medium, high-dose Jiedu-Dihuang Decoction groups and the positive drug group were 1.75±0.10, 1.59±0.11, 1.31±0.11 and 1.48±0.10, respectively; the mRNA expression levels of ASC were 2.69±0.10, 1.96±0.14, 1.54±0.18 and 1.89±0.09, respectively; and the mRNA expression levels of Caspase-1 were 2.85±0.08, 2.24±0.26, 1.58±0.22 and 1.94±0.16, respectively. Except for the low-dose Jiedu-Dihuang Decoction group, the differences between the other treatment groups and the model group were statistically significant (P<0.05, P<0.01). The mean fluorescence intensities of PINK1 in each treatment group were 87.50±9.38, 98.75±7.13, 107.28±6.60 and 94.75±7.11, respectively; those of Parkin were 94.11±8.17, 103.13±8.59, 111.27±9.66 and 101.27±9.21, respectively; and those of Beclin1 were 100.2±7.11, 107.92±6.84, 122.65±8.36 and 105.44±7.55, respectively. Except for the low-dose Jiedu-Dihuang Decoction group, the differences between the other treatment groups and the model group were statistically significant(P<0.05, P<0.01). The proportions of Th1 in peritoneal fluid of each treatment group were (1.34±0.13)%, (1.78±0.21)%, (2.89±0.23)% and (2.47±0.24)%, respectively; and the proportions of Th2 were (1.65±0.18)%, (1.06±0.11)%, (0.57±0.14)% and (0.68±0.07)%, respectively. Except for the low-dose Jiedu-Dihuang Decoction group, the differences between the other treatment groups and the model group were statistically significant (all P<0.05, P<0.01). The levels of IL-4 in peripheral blood of each treatment group were (41.67±4.31), (36.39±5.93), (33.61±4.30) and (33.94±5.81) pg·mL^-1, respectively; those of IL-6 were (39.10±2.89), (32.85±3.98), (28.91±1.91) and (27.63±1.98) pg·mL^-1, respectively; those of IL-10 were (32.11±7.50), (26.28±4.65), (23.22±4.35) and (26.22±6.15) pg·mL^-1, respectively; those of TNF-α were (64.13±13.12), (57.44±13.62), (47.45±10.06) and (50.78±10.9) pg·mL^-1, respectively; those of IL-12 were (34.09±2.49), (38.53±3.84), (42.67±3.87) and (41.93±4.39) ng·mL^-1, respectively; and those of IFN-γ were (286.57±54.77), (358.59±52.15), (435.28±73.12) and (405.33±39.33) pg·mL^-1, respectively. Except for the low-dose Jiedu-Dihuang Decoction group, the differences between the other treatment groups and the model group were statistically significant(all P<0.05, P<0.01)

Jiedu-Dihuang Decoction can improve the inflammatory microenvironment of colon cancer, which may be related to the regulation of NLRP3 inflammasome by mitochondrial autophagy.

To systematically evaluate the efficacy and safety of lecarnitine in the treatment of patients with myocardial damage.

Search databases such as PubMed, Embase, Cochrane Library, CNKI, Wanfang Database, etc. randomized controlled trials (RCTS) comparing L-carnitine with sodium creatine phosphate, sodium fructobisphosphonate, trimetazidine and coenzyme Q10 for the treatment of myocardial damage were included according to the inclusion and exclusion criteria. The search period for all was from the establishment of the database to May 2024. Meta-analysis was performed using RevMan 5.3 and Stata 14.0.

A total of 12 RCTs were included, involving a total of 1 408 patients. Meta-analysis showed that the total effective rate of levocarnitine was 89.53% (556 cases/621 cases), which was significantly higher than that [83.98% (519 cases/618 cases)]of the control group [OR=1.83, 95% CI (1.10~3.06), P<0.05]; the incidence of adverse drug reactions of levocarnitine and the control group was 2.47% (9 cases/364 cases) and 3.31% (12 cases/362 cases) with no statistically significant difference [OR=0.83, 95% CI (0.17~4.18), P>0.05]. The creatine kinase (CK) levels of L-carnitine group and the control group were(203.04±34.59) and (238.28±33.97)U·L^-1, respectvely [OR=-26.81, 95% CI (-47.43~-6.18), P<0.01]; the creatine kinase isoenzyme MB (CK-MB) levels were (21.64±10.76) and (26.71±14.48)U·L^-1, respectvely [OR=-4.19, 95% CI (-6.70~-1.67), P<0.001]were significantly better than those of . There was no statistically significant difference in the levels of lactate dehydrogenase (LDH) and cardiac troponin Ⅰ (cTnⅠ) of L-carnitine compared with the control group (all P>0.05).

The effectiveness of levocarnitine in the treatment of myocardial damage is relatively good, and there are no obvious adverse reactions.

To observe the efficacy and safety of mycophenolate mofetil capsules combined with belimumab injection in the treatment of systemic lupus erythematosus (SLE) with acute kidney injury (AKI).

Patients were divided into control group and treatment group according to random number table method. The control group was treated with mycophenolate mofetil capsules, mycophenolate orally, 0.5 g per time, twice a day. The treatment group was treated with belimumab injection on the basis of control group. Take 10 mg·kg^-1 belimumab injection, dissolve in 250 mL normal saline, intravenous infusion, once every 2 weeks for the first 3 times, and once every 4 weeks thereafter. Both groups were treated for 6 months. Symptom score, inflammatory injury index, renal function index, immune function and clinical efficacy were compared between the two groups, and safety evaluations conducted.

A total of 197 cases were screened, with 127 cases enrolled. The treatment group consisted of 63 cases and the control group consisted of 64 cases. In control group, 4 cases dropped out due to mid course transfer, and 60 cases were included. In treatemnt group, 4 cases dropped out due to giving up treatment, and 59 cases were included. After treatment, the British isles lupus assessment group (BILAG) scores in treatment group and control group were (12.05±2.14) and (17.24±3.27) points, respectively; the systemic lupus erythematosus disease activity index (SLEDAI) scores were (6.41±1.33) and (9.25±1.98) points, respectively; the levels of mannose-binding lectin (MBL) were (62.09±6.10) and (78.34±8.51) ng·L^-1, respectively; the levels of serum creatinine (Scr) were (172.20±21.08) and (228.36±25.42) μmol·L^-1, respectively; the levels of blood urea nitrogen (BUN) were (10.07±1.96) and (15.24±3.17) mmol·L^-1, respectively; the levels of immunoglobulin M (IgM) were (1.17±0.21) and (2.19±0.30) g·L^-1, respectively; the levels of IgG were (5.93±0.89) and (4.87±0.65) g·L^-1, respectively. The above indicators in treatment group showed statistically significant differences compared to control group (all P<0.05). The total clinical effective rates of treatment group and control group were 88.14% (52 cases/59 cases) and 71.67% (43 cases/60 cases), respectively, with treatment group significantly higher than control group (P<0.05). The main adverse drug reactions of control group were elevated transaminase levels, nausea, vomiting and diarrhea; treatment group mainly had elevated transaminase levels, nausea and vomiting, vascular edema and diarrhea. The total incidence of adverse drug reactions in control group and treatment group were 10.00% (6 cases/60 cases) and 13.56% (8 cases/59 cases), respectively, with no statistically significant difference (P>0.05).

Mortimycophanate capsules combined with belimumab injection in the treatment of SLE patients with AKI is effective, can improve clinical symptoms and renal function, reduce inflammation, improve immune function, and has good safety.

To analyze the occurrence and risk factors of acute kidney injury (AKI) in patients with hematologic malignancies who experienced severe delayed excretion after high-dose methotrexate (HD-MTX) chemotherapy, and to explore dose adjustment strategies for reusing HD-MTX in these patients.

A retrospective analysis was conducted on clinical data of hematologic malignancy patients treated with HD-MTX in the hematology and oncology departments. Patients with severe delayed MTX excretion (defined as serum MTX >30 μmol·L^-1 at 24 h, >3 μmol·L^-1 at 48 h, >0.3 μmol·L^-1 at 72 h, or prolonged low-level MTX >0.3 μmol·L^-1 for >6 days) were included. Patients were divided into three groups based on AKI severity, group A was mild AKI, group B was moderate AKT, group C was severe AKI. Statistical methods were used to analyze risk factors for severe excretion delay and AKI.

Among 26 patients (28 HD-MTX cycles) with severe delayed excretion, AKI occurred in all cycles (100.00%). Group A accounted for 21.43% (6 cases/28 cases), Group B accounted for 46.43% (13 cases/28 cases), accounted for 32.14% (9 cases/28 cases). Pre-treatment albumin levels in group A, group B and group C were (42.22±4.63), (39.08±4.3) and (35.25±4.19) g·L^-1. Among patients with moderate/severe AKI, 11 received 19 subsequent HD-MTX cycles at reduced doses (1/3-1× original), with no recurrence of excretion delay or AKI.

Low pre-treatment albumin levels, particularly <35 g·L^-1 are strongly associated with severe MTX-related AKI. Patients with a history of MTX-induced AKI can safely reuse HD-MTX at adjusted doses (based on renal recovery and clinical indicators) without AKI recurrence.

To observe the clinical efficacy and safety of polymyxin B injection combined with sitafloxacin tablets in the treatment of hospital-acquired pneumonia (HAP) caused by extensively drug-resistant Pseudomonas aeruginosa.

Patients with pandrug-resistant pseudomonas aeruginosa (PDR-PA) pneumonia admitted to our hospital were enrolled. According to treatment regimen, patients were divided into control group and treatment group. Patients in the control group received polymyxin B injection at an initial dose of 2.0-2.5 mg·kg^-1, followed by a maintenance dose of 1.25-1.5 mg·kg^-1 every 12 h after the loading dose. Patients in the treatment group received additional oral sitafloxacin tablets at 50-100 mg twice daily on the basis of the above regimen. The duration of antibacterial treatment for both groups was 7 days in principle, with a maximum of 14 days. Clinical efficacy, bacterial clearance rate, inflammatory markers, arterial blood gas and oxygenation parameters, prognosis, and safety profiles were compared between two groups.

A total of 128 patients were included in this study, with 64 cases in each group. After treatment, the total effective rates in the control group and the treatment group were 76.56% (49 cases/64 cases) and 95.31% (61 cases/64 cases), showing a statistically significant difference (P<0.05). After treatment, the total bacterial clearance rates in control and treatment groups were were 73.44% (47 cases/64 cases) and 93.75% (60 cases/64 cases), respectively; the serum levels of procalcitonin (PCT) were (1.42±0.31) and (0.81±0.18) ng·mL^-1, respectively; C-reactive protein (CRP) were (68.14±15.62) and (38.27±12.46) mg·L^-1, respectively; and interleukin-6 (IL-6) were (61.73±14.85) and (38.92±11.77) pg·mL^-1, respectively; the arterial partial pressure of oxygen (PaO₂) were (75.36±7.15) and (88.57±6.93) mmHg, respectively; the arterial partial pressure of carbon dioxide (PaCO₂) were (45.27±4.86) and (39.68±4.25) mmHg, respectively; and the oxygenation index (PaO₂/FiO₂) were 236.48±28.51 and 278.36±31.22, respectively. All of these indicators in treatment group showed statistically significant differences compared to control group (all P<0.05). The 28-day all-cause mortality rates of the control group and the treatment group were 10.94% (7 cases/64 cases) and 4.69% (3 cases/64 cases), respectively; and the length of hospital stay were (15.82±4.27) and (14.97±3.58) d, respectively; with no significant differences between the two groups (all P>0.05). The incidences of total adverse drug reactions in the treatment group and the control group were 18.75% (12 cases/64 cases) and 25.00% (16 cases /64 cases), respectively, with no statistically significant difference between the two groups (P>0.05).

Polymyxin B injection combined with sitafloxacin tablets significantly improves bacterial clearance, reduces inflammatory response, and enhances oxygenation in patients with xDR-PA HAP, while maintaining good safety, indicating its potential clinical utility.