OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

OBJECTIVE: To investigate the safety and efficacy of avatrombopag（AVA） combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia. METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups. RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups. CONCLUSION The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Thrombocytopenia/chemically induced* ; Interleukin-11/therapeutic use* ; Retrospective Studies ; Adult ; Thiophenes/therapeutic use* ; Platelet Count ; Female ; Male ; Middle Aged ; Thiazoles

OBJECTIVE: To investigate the efficacy and safety of stanozolol combined with avatrombopag in the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients with relapsed/refractory tumors. METHODS: Twenty-five patients with relapsed/refractory CIT admitted to the Hematology Department of Xiyuan Hospital, China Academy of Chinese Medical Sciences between March 2023 to December 2023 were enrolled. These patients received a combined therapy of stanozolol and avatrombopag. The clinical efficacy, onset time, changes in platelet levels and blood cell counts before and after treatment, and adverse reactions of patients were evaluated. RESULTS: The combination therapy demonstrated remarkable efficacy with a total effective rate of 100%. Among the 25 patients, 19 achieved complete remission and 6 achieved partial remission. The median onset time was 42.5（range: 35-48）days. The average platelet count of the 25 patients increased from (25.73±17.75)×10⁹/L before treatment to (146.4±49.59)×10⁹/L after 3 months of treatment, with a statistically significant difference ( P < 0.05). 18 patients who previously required platelet transfusion were all weaned off platelet transfusion after 3 months of treatment, with a median time to be free from platelet transfusion was 26 (range: 18-51) days. During the treatment, both neutrophils and hemoglobin exhibited various degrees of elevation. Two patients experienced a slight increase in alanine aminotransferase(ALT) levels, which normalized after treatment with oral hepatoprotective drug. One patient had a PLT increase exceeding 350×10⁹/L, and the treatment with avatrombopag was suspended, and aspirin and other drugs were given to prevent thrombosis. No thrombose events or CIT-related bleeding events were observed in all patients. CONCLUSION The combination therapy of stanozolol and avatrombopag is significantly effective for treating relapsed/refractory CIT patients, with a high response rate and good safety, making it a suitable clinical treatment option.
Humans ; Thrombocytopenia/chemically induced* ; Stanozolol/therapeutic use* ; Male ; Female ; Neoplasms/drug therapy* ; Middle Aged ; Thiophenes/therapeutic use* ; Adult ; Platelet Count ; Treatment Outcome ; Antineoplastic Agents/adverse effects* ; Recurrence ; Thiazoles

OBJECTIVE: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of treatment in patients with acute coronary syndromes (ACS) and in those undergoing percutaneous coronary intervention (PCI). In current clinical situation, availability of different oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) has enabled physicians to switch among therapies owing to specific clinical scenarios. Although optimum time, loading dose and interval of transition between P2Y12 inhibitors is still controversial and needs further evidence, switching between oral inhibitors frequently occurs in clinical practice for several reasons. DATA SOURCES: This review was based on data in articles published in PubMed up to June 2018, with the following keywords "antiplatelet therapy", "ACS", "PCI", "ticagrelor", and "clopidogrel". STUDY SELECTION: Original articles and critical reviews on de-escalation strategy in ACS patients after PCI were selected. References of the retrieved articles were also screened to search for potentially relevant papers. RESULTS: Safety concerns associated with switching between antiplatelet agents, has prompted the use of clopidogrel for patients with ACS especially after PCI as a de-escalation strategy. Practical considerations for de-escalating therapies in patients with ACS such as reducing dose of P2Y12 inhibitors or shortening duration of DAPT (followed by aspirin or P2Y12 receptor inhibitor monotherapy) as potential options are yet to be standardized and validated. CONCLUSIONS Current review will provide an overview of the pharmacology of common P2Y12 inhibitors, definitions of de-escalation and different de-escalating strategies and its outcomes, along with possible direction to be explored in de-escalation.
Acute Coronary Syndrome ; drug therapy ; therapy ; Aspirin ; therapeutic use ; Diamines ; therapeutic use ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; therapeutic use ; Purinergic P2Y Receptor Antagonists ; therapeutic use ; Thiazoles ; therapeutic use

OBJECTIVETo compare the clinical efficacy on knee osteoarthritis (KOA) at the early and middle stage between electroacupuncture (EA) and meloxicam.

METHODSNinety patients of KOA at the early and middle stage were randomized into an EA group and a meloxicam group, 45 cases in each one. In the EA group, EA was applied to Dubi (ST 35), Neixiyan (EX-LE 4), Liangqiu (ST 34), Heding (EX-LE 2), Xuehai (SP 10), Yan- glingquan (GB 34) and Zusanli (ST 36); the needles were retained for 20 min and EA was applied once every two days. In the meloxicam group, the meloxicam tablets were prescribed for oral administration, 7. 5 mg, once a day. The treatment lasted for 6 weeks in the two groups. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score, rectus femoris muscle tension, the 8-foot walking test and 5-time sit-to-stand test were adopted to observe and compare the effects in the two groups.

RESULTSAfter treatment, every item score in WOMAC was reduced after treatment (all P < 0.05), but the difference was not significant between the two groups (all P > 0.05). In the EA group, the rectus femoris tension after treatment was reduced as compared with that before treatment (P < 0.05) and the reducing result was much more apparent as compared with that in the meloxicam group (P < 0.05). For the 8-foot walking test and 5-time sit-to-stand test, the time was shortened after treatment in the two groups (all P < 0.05) and the result in the EA group was much more obvious than that in the meloxicam group (both P < 0.05).

CONCLUSIONBoth EA and meloxicam are effective in the treatment of KOA at the early and middle stage. EA improves rectus femoris tension and recovers the internal mechanics balance and the efficacy is better than that of meloxicam.

Acupuncture Points ; Adult ; Aged ; Electroacupuncture ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; drug therapy ; therapy ; Thiazines ; therapeutic use ; Thiazoles ; therapeutic use ; Treatment Outcome

PURPOSE: The purpose of this study was to define the role of cyclooxygenase-2 inhibitors (COX-2i) in reducing hepatic fibrosis in pediatric patients with chronic liver disease. MATERIALS AND METHODS: From September 2009 to September 2010, patients over 2 years old who visited our outpatient clinic for follow-up to manage their chronic liver disease after Kasai portoenterostomy for biliary atresia, were included in this study. Volunteers were assigned to the study or control groups, according to their preference. A COX-2i was given to only the study group after obtaining consent. The degree of hepatic fibrosis (liver stiffness score, LSS) was prospectively measured using FibroScan, and liver function was examined using serum analysis before and after treatment. After 1 year, changes in LSSs and liver function were compared between the two groups. RESULTS: Twenty-five patients (18 females and 7 males) were enrolled in the study group. The control group included 44 patients (26 females and 18 males). After 1 year, the least square mean values for the LSSs were significantly decreased by 3.91±0.98 kPa (p=0.004) only in the study group. Serum total bilirubin did not decrease significantly in either group. CONCLUSION: COX-2i treatment improved the LSS in patients with chronic liver disease after Kasai portoenterostomy for biliary atresia.
Biliary Atresia/complications/enzymology/*surgery ; Child ; Child, Preschool ; Chronic Disease ; Cyclooxygenase 2 Inhibitors/*therapeutic use ; Female ; Humans ; Liver Cirrhosis/etiology/pathology/*prevention & control ; Male ; *Portoenterostomy, Hepatic ; Thiazines/*therapeutic use ; Thiazoles/*therapeutic use

BACKGROUNDAt present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.

METHODSThis study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.

RESULTSAt week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.

CONCLUSIONSCompared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.

REGISTRATION NUMBERChiCTR-TRC-13003776.

Adult ; Blood Glucose ; drug effects ; C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drug Combinations ; Drug Therapy, Combination ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Metformin ; administration & dosage ; adverse effects ; therapeutic use ; Middle Aged ; Thiazoles ; administration & dosage ; adverse effects ; therapeutic use

No abstract available.
Base Sequence ; Benzamides/therapeutic use ; Bone Marrow/pathology ; Female ; Fusion Proteins, bcr-abl/*genetics ; Humans ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/*genetics ; Middle Aged ; Philadelphia Chromosome ; Piperazines/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Pyrimidines/therapeutic use ; Sequence Analysis, DNA ; Thiazoles/therapeutic use ; Translocation, Genetic

PURPOSE: The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model. MATERIALS AND METHODS: We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma). RESULTS: Diclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85+/-0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs. CONCLUSION: Diclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Butanones/therapeutic use ; Chronic Pain/*drug therapy ; Diclofenac/therapeutic use ; Female ; Muscles/drug effects ; Naproxen/therapeutic use ; Pelvic Floor/*pathology ; Pelvic Pain/*drug therapy ; Piroxicam/therapeutic use ; Rats ; Rats, Wistar ; Thiazines/therapeutic use ; Thiazoles/therapeutic use

BACKGROUNDAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the first steps in the development of multiple organ failure induced by sepsis. A systemic excessive inflammatory reaction is currently the accepted mechanism of the pathogenesis of sepsis. Several studies have suggested a protective role of the peroxisome proliferator activated receptor-β/δ (PPAR-β/δ) in related inflammatory diseases. But the role of PPARβ/δ in ALI remains uncertain. The aim of this study was to investigate the role and possible mechanism of PPARβ/δ in ALI induced by sepsis.

METHODSCecal ligation and puncture (CLP) was used as a sepsis model. Rats were randomly divided into four groups, the control group (CON, n = 6), sham-operation group (SHAM, n = 12), cecal ligation and puncture group (CLP, n = 30), GW501516 group (CLP+GW, n = 25), which underwent CLP and were subcutaneously injected with the PPAR-β/δ agonist GW501516 (0.05 mg/100 g body weight). Survival was monitored to 24 hours after operation. Blood pressure, serum creatinine, blood urea nitrogen, aspartate aminotrasferase and alanine aminotrasferase were measured after CLP. Concentrations of tumor necrosis factor α (TNF-α) and interleukin (IL)-1β in serum were detected by enzyme linked immunosorbent assay (ELISA) kits. Lung tissue samples were stained with H&E and scored according to the degree of inflammation. Bacterial colonies were counted in the peritoneal fluid. Alveolar macrophages were cultured and incubated with GW501516 (0.15 µmol/L) and PPARβ/δ adenovirus and then treated with Lipopolysaccharide (2 µg/ml) for 2 hours. The TNF-α, IL-1β and IL-6 RNA in lung and alveolar macrophages were determined by real-time PCR. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in lung and alveolar macrophages was detected by Western blotting.

RESULTSGW501516 significantly increased the survival of septic rats, decreased histological damage of the lungs, reduced inflammatory cytokines in serum and lung tissues of septic rats and did not increase counts of peritoneal bacteria. In vitro, GW501516 and over-expression of PPARβ/δ attenuated gene expression of TNF-α, IL-1β and IL-6 in alveolar macrophages. Both in vivo and in vitro, PPARβ/δ inhibited the phosphorylation of STAT3.

CONCLUSIONPPARβ/δ plays a protective role in sepsis induced ALI via suppressing excessive inflammation.

Acute Lung Injury ; drug therapy ; etiology ; Animals ; Cells, Cultured ; Male ; PPAR delta ; agonists ; metabolism ; PPAR-beta ; agonists ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sepsis ; complications ; drug therapy ; Thiazoles ; therapeutic use