Adult ; Female ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Rhabdomyolysis ; chemically induced ; diagnosis ; Vindesine ; adverse effects ; therapeutic use

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 evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients. METHODS: The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively. RESULTS: In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides（hyper-TG）> hyper fasting glucose（hyper-FBG）> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups. CONCLUSION The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.
Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Metabolic Syndrome ; Retrospective Studies ; Transplantation, Homologous

OBJECTIVE: To observe the effect of nape cluster acupuncture on swallowing function and respiratory function in patients with post-stroke dysphagia, and to explore its relationship to cerebral arterial flow and neurotrophic factors. METHODS: A total of 120 patients with post-stroke dysphagia were randomized into an observation group and a control group, 60 patients in each one. The conventional swallowing rehabilitation therapy and respiratory function training were adopted in the control group. On the basis of treatment in the control group, nape cluster acupuncture was applied at Fengchi (GB 20), Tianzhu (BL 10), Wangu (GB 12), Lianquan (CV 23), Panglianquan (Extra), once a day; pricking blood was applied at Jinjin (EX-HN 12) and Yuye (EX-HN 13), once every 2 days. Both groups were treated for 2 weeks. The therapeutic efficacy was compared between the two groups, and the swallowing function (scores of Kubota water swallowing test, standardized swallowing assessment [SSA] and video fluoroscopic swallowing study [VFSS]), the respiratory function indexes (forced vital capacity [FVC], maximal voluntary ventilation [MVV] and maximal expiratory time), the bilateral cerebral arterial hemodynamics parameters (systolic peak velocity [Vs], mean flow velocity [Vm] and vascular resistance index [RI]) and the serology indexes (brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF] and insulin-like growth factors-1 [IGF-1]) before and after treatment were observed in the both groups. RESULTS: The total effective rate was 80.0% (48/60) in the observation group, which was superior to 60.0% (36/60) in the control group ( CONCLUSION On the basis of the conventional rehabilitation training, nape cluster acupuncture can effectively improve the swallowing function and respiratory function in patients with post-stroke dysphagia, its mechanism may be related to the improvement of cerebral hemodynamics and the regulation of neurotrophic factors.
Acupuncture Points ; Acupuncture Therapy ; Deglutition ; Deglutition Disorders/therapy* ; Humans ; Treatment Outcome

Objective: To investigate the clinical efficacy of fecal microbiota transplantation (FMT) for treating steroid-refractory gastrointestinal acute graft-versus-host disease (GI-aGVHD) . Methods: This analysis included 29 patients with hematology who developed steroid-refractory GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Huaian Hospital Affiliated to Xuzhou Medical University from March 2017 to March 2022. Among them, 19 patients underwent FMT treatment (the FMT group) and 10 patients did not (the control group). The efficacy and safety of FMT were assessed, as well as the changes in intestinal microbiota abundance, lymphocyte subpopulation ratio, peripheral blood inflammatory cytokines, and GVHD biomarkers before and after FMT treatment. Results: ① Complete remission of clinical symptoms after FMT was achieved by 13 (68.4%) patients and 2 (20.0%) controls, with a statistically significant difference (P<0.05). Intestinal microbiota diversity increased and gradually recovered to normal levels after FMT and FMT-related infections did not occur. ②The proportion of CD3(+) and CD8(+) cells in the FMT group after treatment decreased compared with the control group, and the ratio of CD4(+), regulatory T cells (Treg), and CD4(+)/CD8(+) cells increased (all P< 0.05). The interleukin (IL) -6 concentration in the FMT group was lower than that in the control group [4.15 (1.91-5.71) ng/L vs 6.82 (2.40-8.91) ng/L, P=0.040], and the IL-10 concentration in the FMT group was higher than that in the control group [12.11 (5.69-20.36) ng/L vs 7.51 (4.10-9.58) ng/L, P=0.024]. Islet-derived protein 3α (REG3α) was significantly increased in patients with GI-aGVHD, and the REG3α level in the FMT group was lower than that in the control group after treatment [30.70 (10.50-105.00) μg/L vs 74.35 (33.50-139.50) μg/L, P=0.021]. Conclusion: FMT is a safe and effective method for the treatment of steroid-refractory GI-aGVHD by restoring intestinal microbiota diversity, regulating inflammatory cytokines, and upregulating Treg cells.
Humans ; Fecal Microbiota Transplantation/methods* ; Treatment Outcome ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Steroids

AIMTo explore effects of intrathecal injection of U0126 on morphine withdrawal response and the spinal Phospho-CREB expression in morphine-induced withdrawal rats.

METHODSAll the rats were divided into 5 groups: control group, dependence group, withdrawal group, U0126 group (5 microg, it) and DMSO group. Morphine withdrawal score, touch evoked agitation scores(TEA score), immunohistochemical and Western-blotting technique were used to evaluate morphine withdrawal response and the expression of Phospho-CREB in the spinal cord.

RESULTSIntrathecal injection of MEK inhibitor U0126 significantly alleviated morphine withdrawal symptoms. Morphine withdrawal scores in U0126 group (22.5 +/- 4.09) were significantly lower than that of withdrawal group (28.6 +/- 4.89, P < 0.05). TEA score of withdrawal group was 13.5 +/- 2.55, which was significantly higher than that of U0126 group (10.0 +/- 2.76, P < 0.05). Phospho-CREB positive neurons in the spinal dorsal horn of withdrawal group were 380 +/- 71, which is higher than that of U0126 group (293 +/- 47, P < 0.05). Compared with withdrawal group, level of Phospho-CREB protein detected by Western blot in spinal cord of U0126 group was significantly lower.

CONCLUSIONMEK inhibitors U0126 could suppress expression of Phospho-CREB in the spinal cord.

Animals ; Butadienes ; pharmacology ; therapeutic use ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Injections, Spinal ; Male ; Morphine Dependence ; drug therapy ; metabolism ; Nitriles ; pharmacology ; therapeutic use ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; drug effects ; metabolism ; Substance Withdrawal Syndrome ; drug therapy ; metabolism

OBJECTIVETo investigate the effects of administration of dexmedetomidine in anaesthesia for esophageal cancer operation.

METHODS100 patients (ASAI-II) who were undergoing to esophageal cancer operation were randomly divided into control group (group A) and dexmedetomidine group (group B) (n = 50). The scheme of induction and maintenance of aesthesia of the two groups were identical. Patients in group B administered dexmedetomidine at a dose of 1 microg/kg over 10 min and patients in group A were given a placebo infusion of normal saline. Patients in group B administered dexmedetomidine at a dose of 0.4 microg/(kg x h) was injected and stoped at 30 min by the end of operation. Mean artery pressure (MAP) and heart rate (HR) were detected before induction (T0), induction (T1), 1 min after extubation (T2), 5 min after extubation (T3) and 10 min after extubation (T4) Propofol comsumption, fentanlyl comsumption, and side effects were recorded as well.

RESULTSThe results showed that MAP and HR (T0, T1, T2, T3, T4) in group B were significantly different from those in group A which fluctuated more markedly (P < 0.05). Propofol comsumption in group A was much more than that in group B (P < 0.05). Incidence of pharynx and larynx ache and restlessness were higher in group A than those in group B (P < 0.05).

CONCLUSIONDexmedetomidine could effectively reduce the cardiovascular response to incubation and extubation in esophageal cancer operation patients. Propofol comsumption, fentanlyl comsumption and side effects were reduceed as well.

Adjuvants, Anesthesia ; administration & dosage ; Adult ; Aged ; Analgesics, Non-Narcotic ; administration & dosage ; Anesthetics, Intravenous ; administration & dosage ; Dexmedetomidine ; administration & dosage ; Esophageal Neoplasms ; surgery ; Female ; Fentanyl ; administration & dosage ; Humans ; Male ; Middle Aged ; Propofol ; administration & dosage

OBJECTIVETo explore the effects of intrathecal injection of mitogen-activated protein kinases inhibitors U0126 on the behavioral changes of morphine-induced dependent and withdrawal rats and the expression of nitric oxide synthase (NOS) in spinal cord.

METHODSAll the rats were divided into 4 groups: control group, dependent group, withdrawal group, U0126 group (5 microg). Global withdrawal score, Touch evoked agitation scores (TEA score), immunohistochemical and Western blot technique were undertaken to evaluate behavioral changes and expression of FOS, nNOS and iNOS in spinal cord respectively.

RESULTSThe results showed that intrathecal administration of U0126 significantly alleviated withdrawal symptom, withdrawal scores of U0126 group (22.5 +/- 4.09) were significantly lower than than those of withdrawal group (28.6 +/- 4.89) (P < 0.05). TEA scores of withdrawal group were 13.5 +/- 2.55, which were significantly higher than those of U0126 group (10.0 +/- 2.76, P < 0.05). Fos-like positive neurons in dorsal horn of withdrawal group were 380 +/- 71, which were higher than those of U0126 group(287 +/- 54, P < 0.05). Also nNOS and iNOS positive neurons in dorsal horn of U0126 group were 180 +/- 32, 10.8 +/- 2.8 respectively, which were significantly lower than that of withdrawal group (239 +/- 45, 16.8 +/- 5.1, P < 0.05). Compared with withdrawal group, levels of nNOS and iNOS protein in spinal cord of U0126 group were significantly lower.

CONCLUSIONMEK inhibitors could alleviate withdrawal symptom of morphine-induced dependent rats and could suppress expression of NOS in spinal cord, and extracellular signal-regulate kinase (ERK) might involve the expression of NOS in spinal cord.

Animals ; Behavior, Animal ; drug effects ; Butadienes ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Male ; Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; Morphine ; adverse effects ; Morphine Dependence ; metabolism ; Nitric Oxide Synthase ; metabolism ; Nitriles ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; metabolism ; Substance Withdrawal Syndrome ; metabolism

OBJECTIVETo explore if induced nitric oxide in the spinal cord mediates withdrawal syndrome in morphine-dependent rats.

METHODSMale SD rats weighing 200-250 g were employed in the present study. To set up morphine dependence model, rats were subcutaneously injected with morphine (twice a day, for 5 d). The dose of morphine was 10 mg/kg in the first day and was increased by 10 mg/kg each day. On day 6, 4 h after the injection of morphine (50 mg/kg), morphine withdrawal syndrome was precipitated by an injection of naloxone (4 mg/kg, ip). Inducible nitric oxide synthase (iNOS) inhibitors aminoguanidine (AG) was intrathecally injected 30 min before the administration of naloxone. All the rats were divided into four groups: control group, dependence group, withdrawal group, AG group. Morphine withdrawal score, touch evoked agitation scores (TEA scores), immunohistochemical and Western blot technique were used to evaluate morphine withdrawal response and the expression of iNOS in the spinal cord.

RESULTSIntrathecal injection of iNOS inhibitors AG could alleviate morphine withdrawal symptoms. Morphine withdrawal scores and touch evoked agitation scores in AG group were significantly lower than that of withdrawal group (P < 0.05). iNOS positive neurons in dorsal horn of AG group were significantly lower than that of withdrawal group (P < 0.05). Level of iNOS protein in spinal cord of AG group was significantly lower than that of withdrawal group (P < 0.05).

CONCLUSIONInduced nitric oxide in the spinal cord may mediate withdrawal syndrome in morphine-dependent rats.

Animals ; Male ; Morphine Dependence ; metabolism ; Naloxone ; pharmacology ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; metabolism ; Substance Withdrawal Syndrome ; metabolism

OBJECTIVETo investigate the effect of P2X7R antagonist brilliant blue G (BBG) on aGVDH of mice after allo-HSCT.

METHODSaGVHD mouse model after HSCT was established and treated with the P2X7R antagonist BBG of different dosages (50 mg/kg and 75 mg/kg). After treatment, the survival, body weight, pathological and liver function of aGVDH mice were abserved, and the expression levels of P2X7, NLRP3, caspase-1, IL-1β, IL-18 mRNA and protein were evaluated by real-time PCR and Western blot.

RESULTSThe allo-HSCT aGVHD mouse model was successfully established, the intraperitoneal injection of BBG alleviated the aGVHD clinical manifestations including roachback, ruffled fur, skin peeling and weight loss of recipient mice, decreased P2X7R and IL-1β expression and reduced the mRNA levels of P2X7R, NLRP3, Caspase-1, IL-1β and IL-18. Furthermore, GVHD group receiving 75 mg/kg BBG showed most significant difference of these indexes.

CONCLUSIONBBG alleviates liver inflammatory damage induced by aGVHD after allo-HSCT, and decreases the expression of proinflammatory cytokines. Moreover, the protective effect of that of BBG 75 mg/kg group is better than that of BBG 50 mg/kg group.