Airway Extubation ; adverse effects ; Bridged Bicyclo Compounds, Heterocyclic ; therapeutic use ; Endoscopy ; Humans ; Nasal Surgical Procedures ; Tetrahydronaphthalenes ; therapeutic use ; Trachea

OBJECTIVE: To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored. RESULTS: The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients. CONCLUSION VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.
Adult ; Humans ; Retrospective Studies ; Neoplasm, Residual/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Recurrence ; Leukemia, Myeloid, Acute/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

OBJECTIVE: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）. METHODS: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed. RESULTS: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients. CONCLUSION VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Nucleophosmin ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Leukemia, Myeloid, Acute/genetics* ; Recurrence ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

BACKGROUNDThe hairpin cell-penetrating peptides (hCPPs) demonstrate an interesting characteristic of conditioned activation by molecules. We hypothesized that hCPPs have the potential to selectively deliver a paramagnetic gadolinium probe into the matrix metalloproteinase 2 (MMP-2) positive human ovary adenocarcinoma cell lines, SKOV-3.

METHODShCPPs were synthesized and labeled with 1,4,7,10-tetraazacyclododecane-N,N',N'',N''' tetraacetic acid gadolinium (III) (Gd-DOTA) and fluorescein isothiocyanate (FITC) by f-moc strategy using a standard solid phase peptide synthesis protocol. MMP-2 expression and activity were demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR) and zymography. Internalization and location of hCPPs in SKOV-3 cells were observed by fluorescein imaging and flow cytometery. Selective delivery of Gd-DOTA in SKOV-3 cells was observed by magnetic resonance imaging (MRI) and transmission electron microscopy (TEM).

RESULTSThe uptake of hCPPs by SKOV-3 cells depended on the activity of MMP-2. T1WI signals of SKOV-3 cells treated with Gd-DOTA-hCPPs suggested the uptake of Gd-DOTA-hCPPs increased in a time- (r = 0.990, P < 0.01) and concentration-dependent manner (r = 0.964, P < 0.001), but was inhibited by a MMP-2 inhibitor. Electron-dense particles observed in the cytoplasm and nucleus by transmission electron microscopy proved the intracellular penetration of gadolinium.

CONCLUSIONShCPPs can be used as an effective vector for an MRI molecular probe to assess the activity of MMP-2.

Cell Line, Tumor ; Cell-Penetrating Peptides ; adverse effects ; chemical synthesis ; chemistry ; metabolism ; Flow Cytometry ; Heterocyclic Compounds ; adverse effects ; chemical synthesis ; chemistry ; metabolism ; Humans ; Magnetic Resonance Imaging ; Matrix Metalloproteinase 2 ; chemistry ; metabolism ; Microscopy, Electron, Transmission ; Organometallic Compounds ; adverse effects ; chemical synthesis ; chemistry ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo evaluate the efficacy and safety of patient-controlled intravenous analgesia (PCIA) of dezocine combined with sufentanil in burn patients after escharectomy or tangential excision followed by autologous skin grafting.

METHODSSixty burn patients hospitalized in Department of Burns and Plastic Surgery of our hospital from February 2011 to December 2013, conforming to the study criteria and going to have escharectomy or tangential excision followed by autologous skin grafting, were divided into sufentanil group (S, n = 30) and dezocine+sufentanil group (DS, n = 30) according to the random number table. Patients in group S were given 150 mL normal saline containing 2.5 µg/kg sufentanil citrate and 6 mg tropisetron after skin grafting for 48 hours. Patients in group DS were given 150 mL normal saline containing 0.25 mg/kg dezocine, 1.5 µg/kg sufentanil citrate, and 6 mg tropisetron for 48 hours. Visual Analog Scale (VAS), Bruggrmann Comfort Scale (BCS), and Ramsay Sedation Scale were used to evaluate the sedative effect or analgesic effect, and their scores were recorded at administration hour (AH) 2, 6, 12, 24, and 48. The times of efficient injection and incidence of adverse effect within the 48 AH were recorded. Data were processed with analysis of variance for repeated measurement, t test, chi-square test, and Fisher's exact test.

RESULTSThere were no obvious differences in the scores of VAS and BCS between two groups at each time point (with t values from -0.426 to 0.864, P values above 0.05). The scores of Ramsay Sedation Scale in group S at AH 2, 6, 12, 24, and 48 were respectively (3.2 ± 0.6), (3.2 ± 0.5), (3.3 ± 0.7), (3.2 ± 0.4), and (3.3 ± 0.4) points, which were higher than those in group DS [(2.4 ± 0.6), (2.5 ± 0.5), (2.4 ± 0.6), (2.4 ± 0.4), and (2.4 ± 0.5) points, with t values from 5.302 to 8.391, P values below 0.001]. The times of efficient injection within the 48 AH was 6.8 ± 0.7 in group S and 6.5 ± 0.9 in group DS, showing no significantly statistical difference (t = 1.260, P > 0.05). Respiratory depression was not observed in both groups; the incidence of pruritus was the same, and that of urine retention was similar between the 2 groups within the 48 AH (with P values above 0.05). Within the 48 AH, the incidence of nausea and vomiting in group S was 26.7% (8/30), which was obviously higher than that in group DS (6.7%, 2/30, P < 0.05); the incidence of drowsiness in group S was 20.0% (6/30), which was significantly higher than that in group DS (no patient, P < 0.05).

CONCLUSIONSDezocine combined with sufentanil can provide effective postoperative analgesia with little adverse effect for PCIA in burn patients after escharectomy or tangential excision followed by autologous skin grafting, therefore it can be widely used.

Analgesia, Patient-Controlled ; adverse effects ; Analgesics, Opioid ; administration & dosage ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; adverse effects ; Burns ; surgery ; Female ; Humans ; Hypnotics and Sedatives ; administration & dosage ; Infusions, Intravenous ; Male ; Pain, Postoperative ; drug therapy ; Reconstructive Surgical Procedures ; Skin Transplantation ; Sufentanil ; administration & dosage ; adverse effects ; Tetrahydronaphthalenes ; administration & dosage ; adverse effects ; Treatment Outcome

PURPOSE: We compared the prophylactic effects of intravenously administered azasetron (10 mg) and ondansetron (8 mg) on postoperative nausea and vomiting (PONV) in patients undergoing gynecological laparoscopic surgery under general anesthesia. MATERIALS AND METHODS: We studied 98 ASA physical status I or II 20-65 years old, female patients, in this prospective, randomized, double blind study. Patients were randomly divided into two groups and received ondansetron 8 mg (group O) or azasetron 10 mg (group A) 5 min before the end of surgery. The incidence of PONV, Visual Analogue Scale (VAS) for pain, need for rescue antiemetic and analgesics, and adverse effects were checked at 1, 6, 12, 24, and 48 h postoperatively. RESULTS: The overall incidence of PONV was 65% in group O and 49% in group A. The incidence of PONV was significantly higher in group O than in group A at 12-24 h postoperatively (nausea; 24% vs. 45%, p = 0.035, vomiting; 2% vs. 18%, p = 0.008), but there were no significant differences at 0-1, 1-6, 6-12 or 24-48 h. CONCLUSION: In conclusion, azasetron (10 mg) produced same incidence of PONV as ondansetron (8 mg) in patients undergoing general anesthesia for gynecological laparoscopic surgery. Azasetron was more effective, in the intermediate post-operative period, between 12 and 24 h.
Adult ; Aged ; Bicyclo Compounds, Heterocyclic/*therapeutic use ; Female ; Gynecologic Surgical Procedures/*adverse effects ; Humans ; Middle Aged ; Ondansetron/*therapeutic use ; Oxazines/*therapeutic use ; Postoperative Nausea and Vomiting/*prevention & control ; Serotonin Antagonists/*therapeutic use ; Treatment Outcome ; Young Adult

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.
Humans ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Hematopoietic Stem Cell Transplantation ; Heterocyclic Compounds/adverse effects* ; Lymphoma/drug therapy* ; Lymphoma, T-Cell/therapy* ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Transplantation, Autologous

OBJECTIVETo investigate the impact of the mobilization with the antagonist of the stromal cell-derived factor receptor CXCR4 (AMD3100) (plerixafor), granulocyte-colony-stimulating factor (G-CSF) alone and in combination on the proliferation and cytotoxic functions of the murine splenic lymphocytes.

METHODSC57BL/6(H-2(b)) mice, as donors, were mobilized by, AMD3100, G-CSF alone or in combination (n = 10 mice in each group), and phosphate buffered saline (PBS). Then, the proliferation capacity of murine lymphocytes either in response to the phytohemagglutinin (PHA) stimulation or the mixed lymphocytes reaction (MLR) with allo-lymphocytes from the BALB/C(H-2(d)) mice were detected by CCK-8 method. The cytotoxic capacity of murine lymphocytes on Yac-1 tumor cells was examined by LDH assay.

RESULTSThe proliferation capacity and the responsiveness to alloantigen of the lymphocytes derived from the mice spleen mobilized by AMD3100, G-CSF alone or in combination were significantly lower than those by PBS control (P < 0.05), and those combination of AMD 3100 and G-CSF group were significantly lower than in other groups(P < 0.05). At the effector-target ration of 40:1, the cytotoxic capacity of murine lymphocytes in above mobilization groups was lower than in control group, but no statistically significant difference (P > 0.05).

CONCLUSIONBoth the proliferation capacity and the responsiveness to alloantigen of the murine lymphocytes decreases significantly after the mobilization with AMD3100, G-CSF alone or in combination, whereas no significant alternations are demonstrated on the cytotoxic capacity of murine lymphocytes. Further studies are needed to clarify the underlying mechanisms.

Animals ; Cell Proliferation ; Granulocyte Colony-Stimulating Factor ; adverse effects ; pharmacology ; Hematopoietic Stem Cell Mobilization ; methods ; Hematopoietic Stem Cell Transplantation ; methods ; Heterocyclic Compounds ; administration & dosage ; pharmacology ; Lymphocytes ; drug effects ; immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Receptors, CXCR4 ; drug effects ; Sincalide

OBJECTIVETo observe the effects of Biannaitong Medicinal Tea (BNT) combined with Azasetron in preventing and treating the gastrointestinal reaction induced by chemotherapy.

METHODSSixty-four patients underwent chemotherapy with DP regimen (docetaxol + DDP) were randomly assigned to two groups, the treated group and the control group. All patients were given 10 mg Azasetron intravenously 30 min before starting chemotherapy once a day for two successive days, but to patients in the treated group, 300 mL BNT was given orally additionally in the evenings before chemotherapy. The occurrence of adverse reactions, such as antiemetic efficacy constipation, abdominal distention, etc. was observed.

RESULTSThe vomiting control rates in the two groups were insignificantly different (87.5% vs 84.4%, P > 0.05), but difference in the complete control rates between them were significant (53.1% vs 43.8% , P < 0.05). And the occurrences of constipation (3.1% vs 59.4%) and abdominal distention (15.6% vs 59.4%) in the two groups were also significantly different (both P <0.05).

CONCLUSIONBNT used in coordination with Azasetron for alleviating vomiting could enhance the antiemetic effect, reduce the adverse effects of chemotherapy, such as constipation, abdominal distension and anorexia, and thus to increase the compliance of patients.

Adult ; Aged ; Anorexia ; chemically induced ; prevention & control ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bridged Bicyclo Compounds, Heterocyclic ; therapeutic use ; Constipation ; chemically induced ; prevention & control ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Neoplasms ; drug therapy ; Oxazines ; therapeutic use ; Phytotherapy ; Serotonin Antagonists ; therapeutic use ; Treatment Outcome

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.
Antiviral Agents/therapeutic use* ; Carbamates ; Drug Therapy, Combination ; Genotype ; Hepacivirus/genetics* ; Hepatitis C/drug therapy* ; Hepatitis C, Chronic/drug therapy* ; Heterocyclic Compounds, 4 or More Rings ; Humans ; Liver Cirrhosis/complications* ; Prospective Studies ; RNA ; Ribavirin/therapeutic use* ; Sofosbuvir/adverse effects* ; Sustained Virologic Response ; Treatment Outcome