Objective To establish a UPLC-MS/MS method for the determination of nilotinib in human plasma.Methods The plasma procedure involved a single-step protein precipitation by acetonitrile, then separation was carried out using a ACQUITY UPLC BEH C18 column ( 100 mm ×2.1 mm, 1.7 μm) with a mobile phase consisted of acetonitrile -0.1% formic acid ( 35∶65 ) at a flow rate of 0.4 mL? min -1 .The protonated ions of analytes were detected in positive ionization by multiple reaction monitoring mode ( MRM ) .The speci-ficity, standard curve, lower limit of quantitation, precision, recovery rate and stability as well as the matrix effect were investigated. Results The calibration curve was linear over a concentration range of 0.1 to 20.0 μg? mL -1 ( r=0.998) and the low limit of quantita-tion was 0.1 μg? mL -1 .The extraction recovery rates were ranged from 95.11% to 101.32%, with-day RSD and between-day RSD were all less than 15%.Conclusion The method is simple and quick, with high specificity and sensitivity, and suitable for clinical therapeutic drug monitoring of nilotinib.

BACKGROUNDXiaobuxin-Tang, a traditional Chinese herbal prescription recorded in a silk scroll unearthed from Mogao Caves of Dunhuang has been indicated that it can remit depressive disorder. The present study was designed to investigate its antidepressant effects in various animal depression models.

METHODSXiaobuxin-Tang was extracted by 70% alcohol, and then three behavioral despair models and 5-Hydroxytryptophan (HTP)-induced head twitch response model were adopted to assess the antidepressant effects of the ethanolic extract of Xiaobuxin-Tang with the study on spontaneous motor activity. Groups of mice and rats received oral treatment with Xiaobuxin-Tang (150 - 1200 mg/kg) only once acutely in all tests. The duration of immobility was measured during the last 4 minutes of the 6-minutes test period in mice forced swimming test, rats forced swimming test and mice tail suspension test. In 5-HTP-induced head twitch response, the mice were intraperitoneally administered with 120 mg/kg of L-5-HTP, and then the cumulative number of head twitches was counted in 20 minutes. Spontaneous motor activities of mice were recorded automatically in 10 minutes by VIDEOMEX-V image analytic system.

RESULTSThe extract at doses of 300 mg/kg (p.o.) and 600 mg/kg (p.o.) significantly decreased the duration of immobility time in a dose dependent manner in mice forced swimming test; also, the extract at dose of 1200 mg/kg (p.o.) significantly decreased the duration of immobility time in rat forced swimming test. Furthermore, the extract at a dose of 600 mg/kg had the same effect in mice tail suspension test. Meanwhile, the extract at the effective doses for behavioral despair models, had no effect on spontaneous motor activity in mice. The extract (300 - 1200 mg/kg, p.o.) also increased the accumulative number of the 5-HTP-induced head twitch response in mice in 20 minutes.

CONCLUSIONOur results suggested that the ethanolic extract of Xiaobuxin-Tang exerts antidepressant-like effect.

Animals ; Antidepressive Agents ; pharmacology ; Depression ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Hindlimb Suspension ; Male ; Mice ; Mice, Inbred ICR ; Motor Activity ; drug effects ; Swimming

OBJECTIVETo objectively evaluate the efficacy and safety of Yimusake Tablet in the treatment of premature ejaculation (PE) through a multi-centered large-sample trial.

METHODSWe conducted a multi-centered, open, fixed-dose, and self-compared clinical trial among 300 patients with diagnosed PE. The trial lasted 12 weeks, including 4 weeks without any medication and 8 weeks of treatment with Yimusake Tablet, 2 pills (1 g) per night. We observed the intravaginal ejaculation latency time (IELT) before and after treatment, evaluated the safety of medication, and performed a questionnaire investigation on the patients' satisfaction.

RESULTSOf the 300 PE patients, 288 accomplished the clinical trial. The patients ranged in age from 22 to 60 years, averaging at 31.6 years. The mean IELT of the patient was 62.5 seconds at baseline, 168.9 seconds after 4 weeks of treatment with Yimusake Tablet, and 222.2 seconds after 8 weeks of medication. Among the 157 patients with normal erectile function (IIEF >21), the mean IELT was 71.4 seconds before treatment, 147.4 seconds after 4 weeks of medication, and 172.5 seconds after 8 weeks of medication. The patients' satisfaction was significantly increased after treatment. Those complicated by mild to moderate erectile dysfunction achieved different degrees of improvement in the IIEF-5 score, with a mean increase of 3.8. Only a few patients experienced mild adverse events, including constipation, dry mouth, nose bleeding, abdominal pain, and lumbosacral pain, which were all relieved without drug withdrawal.

CONCLUSIONYimusake Tablet is a safe and effective medicine for the treatment of PE.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Ejaculation ; drug effects ; physiology ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Middle Aged ; Patient Satisfaction ; Penile Erection ; Phytotherapy ; Premature Ejaculation ; drug therapy ; Surveys and Questionnaires ; Tablets ; Time Factors

OBJECTIVETo evaluate the learning curve of complete mesocolic excision(CME) for colon cancer.

METHODSClinical data of 75 cases in whom CME was performed by a group of surgeons in the Department of Gastrointestinal Surgery, Peking University People's Hospital from November 2009 to June 2011 were reviewed. The patients were divided into three groups(groups A, B, C, 25 cases in each group) by operative chronologic sequence.

RESULTSThere were no significant differences in age, sex, preoperative staging, cancer location, operation history of abdomen, ASA among the three groups(P>0.05). The operative time in group A was (205.4 ± 53.2) min and decreased to (180.4 ± 29.7) min in group B and (169.8 ± 41.3) min in group C (P<0.05). The postoperative hospital stay decreased from (17.8 ± 10.9) d in group A to(12.9 ± 4.1) d in group B and(11.0 ± 3.5) d in group C(P<0.05). The postoperative complication rate decreased from 32%(8/25) in group A and 36%(9/25) to 8%(2/25) in group C. The specimen quality was superior in group C compared to group A (WEST grade C above were 20 and 11 respectively, P<0.05). There were no significant differences in intraoperative bleeding, time to first flatus, postoperative fasting time, number of retrieved lymph nodes among the three groups(P>0.05).

CONCLUSIONFrom the learning curve of CME, surgeons can learn CME skill after performing 25 cases.

Adult ; Aged ; Aged, 80 and over ; Colectomy ; education ; methods ; Colonic Neoplasms ; surgery ; Female ; Humans ; Learning Curve ; Male ; Mesocolon ; surgery ; Middle Aged ; Retrospective Studies ; Young Adult

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Carcinoma, Adenoid Cystic ; Humans ; Neoplastic Syndromes, Hereditary ; Skin Neoplasms

Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.

OBJECTIVE: To retrospectively analyze the clinical characteristics and prognostic factors of patients with primary cutaneous lymphoma. METHODS: The clinical data of 22 patients with primary cutaneous lymphoma admitted to Xinjiang Hotan District People's Hospital, Heji Hospital affiliated to Changzhi Medical College and the Fifth Medical Center of PLA General Hospital from January 2013 to June 2021 were retrospectively analyzed. RESULTS: The incidence of primary cutaneous T cell and NK/T cell lymphoma was about 91.9/100 000, and the incidence of primary cutaneous B cell lymphoma was about 14.5/100 000. The overall survival (OS) of patients aged ≥65 years was significantly shorter than that of patients younger than 65 years (P <0.05). Patients with elevated β₂-microglobulin (β₂-MG) had shorter OS and progression-free survival (PFS) (both P <0.05). Patients who achieved complete/partial response after initial treatment had longer OS than those with stable or progressive disease (P <0.05). There were significant differences in OS and PFS among patients with different pathological types of primary cutaneous lymphoma that originated from T and NK/T cells, the OS and PFS of patients with mycosis fungoides were longer than those of patients with other pathological types (both P <0.05). In addition, disease stage might also affect the PFS of the patients (P =0.056). CONCLUSION The age, disease stage, β₂-MG level, pathological type and remission state after treatment of the patients were related to the clinical prognosis.
Humans ; Prognosis ; Retrospective Studies ; Remission Induction ; Lymphoma